Multimodality approach to treat calciphylaxis in end-stage kidney disease patients

Figures & data

Figure 1. Cohort selection flow diagram.

Table 1. Patients characteristics and therapeutic profiles.

Pt	Age (Gender)	Dialysis vintage (months)	Lesion(s) site(s)	Diagnosis Method	Comorbidities	Intravenous Iron	Warfarin	Body mass Index
1	72 (F)	12	Abdomen	Skin biopsy	T2D, hypertension, CAD, PVD, CF, AF, DLP, gout	Yes	Yes	37.88
2	70 (M)	60	Abdomen, right leg	Skin biopsy	T2D, hypertension, CAD, primary hyperparathyroidism	Yes	No	44.75
3	64 (F)	None	Inferior limbs	Skin biopsy	T2D, heart transplant, DVT, episodic hypercalcemia, hypothyroidism, gout	No	Yes	19.84
4	70 (F)	12	Breast	Skin biopsy, mammography	T2D, AF, hypertension, PVD	Yes	Yes	37.46
5	48 (M)	156	Right calf	Skin biopsy	T2D, prior kidney transplant, MGUS-sarcoidosis, AF, PE, hypertension, DLP	Yes	Yes	26.48
6	48 (F)	84	Abdomen, thighs	Skin biopsy	T2D, CAD, PVD, hypertension, gout	No	No	29.40
7	68 (F)	None	Left thigh	Bone scan	T2D, hypertension, prior kidney transplant, CAD, DLP, IBS	No	No	45.45
8	76 (F)	48	Inferior limbs	Skin biopsy, bone scan	T2D, hypertension, CAD, AF, DLP, DISH	Yes	Yes	28.13
9	57 (M)	36	Inferior limbs	Bone scan	T2D, hypertension, CAD, DLP, hypothyroidism, osteoporosis	Yes	Yes	36.73
10	59 (M)	36	Right calf	Skin biopsy	T2D, hypertension, CAD, DLP, PVD	Yes	Yes	36.36
11	82 (F)	None	Inferior limbs	Skin biopsy, bone scan	hypertension, CAD, AF, DLP, COPD	No	Yes	19.69
12	64 (F)	84	Abdomen, thighs	Bone scan	T2D, hypertension, CAD, DLP, prior kidney transplant, hypothyroidism, gout	Yes	Yes	38.87

AF: atrial fibrillation; CAD: Coronary artery disease; CF: Cardiac failure; DISH: Diffuse idiopathic skeletal hyperostosis; DLP: Dyslipidemia; COPD: chronic obstructive pulmonary disease; DVT: Deep vein thrombosis; F: Female; IBS: Irritable bowel syndrome; M: Male; MGUS: Monoclonal gammopathy of undetermined significance; PE: Pulmonary embolism; Pt: Patient; PVD: Peripheral vascular disease; T2D: Type 2 diabetes.

Table 2. Serum biochemical analyses at diagnosis.

Parameter	Mean ± standard deviation
Calcium (mmol/L)	2.15 ± 0.15
Phosphorus (mmol/L)	1.51 ± 0.3
Alkaline phosphatase (IU/L)	118.33 ± 74.78
Intact parathyroid hormone^a (pmol/L)	403.81 ± 244.07
Albumin (g/L)	35.09 ± 3.92
Ferritin (μg/L)	321.60 ± 217.89
Glycated hemoglobin (HbA1c), %	6.93 ± 1.20

^a The value for each patient represents the average of measures conducted during the 12 months prior to the calciphylaxis diagnosis (1–5 measures for each patient) n = 8–12 patients.

Table 3. Clinical responses to sodium thiosulfate, side effects and multimodal interventions.

Patient	Complete response (delay in days)	Partial response (delay in days)	Total dose to complete response (g)	Sodium thiosulfate initiation delay (days)	Side effects	Adjunctive treatments and interventions
1	Yes (NA)	Yes (9)	450	27	Nausea-vomiting, dyspnea, volume overload	Non-calcium chelator, ↑ hemodialysis frequency and duration
2	Yes (115)	Yes (1)	1700	123	Nausea-vomiting, anorexia, weight loss, hypoglycemia	Bisphosphonate, cinacalcet, ↑ hemodialysis frequency
3	Yes (225)	Yes (30)	1650	47	Not documented	None
4	No	Yes (23)	NA	107	Volume overload	Bisphosphonate, ↑ hemodialysis frequency and duration, ↓ calcium dialysate
5	Yes (105)	Yes (NA)	750	13	None	Bisphosphonate
6	No	Yes (4)	NA	273	Nausea-vomiting	Bisphosphonate, cinacalcet, ↑ hemodialysis frequency, ↓ calcium dialysate
7	NA^a	Yes (1)	NA^a	1	Nausea-vomiting, headache, mild hypernatremia	None
8	NA^a	NA	NA^a	8	Nausea-vomiting	Non-calcium chelator, bisphosphonate,↓ calcium dialysate
9	Yes (133)	Yes (3)	1095	14	Volume overload, metabolic acidosis	Non-calcium chelator, bisphosphonate, ↑ hemodialysis frequency and duration, ↓ calcium dialysate
10	NA^a	NA	NA^a	40	Not documented	↓ calcium dialysate
11	No	No	NA	13	None	Bisphosphonate, cinacalcet
12	No	Yes (7)	NA	4	Nausea-vomiting	Non-calcium chelator, bisphosphonate, ↓ calcium dialysate

NA: Not applicable or not available; ↑: Increase; ↓: Decrease

^a Sodium thiosulfate stopped for side effects.

Table 4. No factor was associated with a complete response to sodium thiosulfate treatment.

Patients profile and interventions	Partial response (n = 4)	Complete response (n = 5)	p Value
Age (Mean ± SD, years)	62.50 ± 8.65	62.20 ± 8.82	0.97
Body mass index (Mean ± SD, kg/m^2)	37.80 ± 5.71	33.14 ± 8.85	0.45
Obesity n (%)	3 (75)	3 (60)	1.00
Female n (%)	4 (100)	2 (40)	0.17
Bisphosphonate addition n (%)	3 (75)	3 (60)	1.00
↓ Calcium dialysate (Mean difference ± SE, mmol/L)	−0.07 ± 0.06	−0.16 ± 0.23	0.56
↑ Dialysis frequency (Mean ± SD, per week)	5.0 ± 2.3	3.0 ± 0	0.17
↑ Dialysis duration (Mean ± SD, hours)	3.50 ± 0.71	5.00 ± 2.04	0.39
Post-diagnosis sodium thiosulfate initiation delay (Mean ± SD, days)	96.25 ± 110.61	44.80 ± 40.98	0.42
Sodium thiosulfate treatment duration (Mean ± SD, days)	80.75 ± 46.64	102.20 ± 36.06	0.51

SE: Standard error; SD: standard deviation.