Renal complications in patients with chronic hypoparathyroidism receiving conventional therapy: A systematic literature review

Elvira Gosmanova; Pascal Houillier; John Bilezikian; Claudio Marelli; Lars Rejnmark

doi:10.1530/endoabs.70.AEP212

Conventional therapy for chronic hypoparathyroidism is oral calcium and active vitamin D; despite treatment, chronic hypoparathyroidism may be associated with increased risk of renal complications. Without the effect of parathyroid hormone on renal tubular reabsorption, calcium-conserving and phosphaturic effects are lost, serum calcium levels are reduced and serum phosphate levels are increased. This may lead to hypercalciuria and hyperphosphataemia, which may be associated with long-term renal complications. A systematic literature review was performed to summarise the frequency and nature of renal complications in patients with chronic hypoparathyroidism managed with conventional therapy. Abstracts with specified MeSH terms were identified using the PubMed, EMBASE, and Cochrane databases. Pre-defined outcomes were nephrolithiasis, nephrocalcinosis, and chronic kidney disease (CKD). Papers that described estimated glomerular filtration rate (eGFR) were also selected. The search yielded 1200 articles; following screening and assessment for eligibility, 21 articles reported data for nephrolithiasis/kidney stones, nephrocalcinosis, and/or CKD. Data were extracted from 13 manuscripts with renal outcomes for ≥10 adult (n = 11 manuscripts) or paediatric (n = 2 manuscripts) patients. Some articles contributed to ≥1 outcome category. Due to the heterogeneity of the studies, a meta-analysis could not be conducted. The reported rate of nephrolithiasis was ≤36%, including 0% in the Levy et al paediatric study, with low rates in other studies reporting shorter duration of disease (Table). Nephrocalcinosis was ≤ 38%, with 2 studies reporting rates of 0% (Table). Nephrolithiasis and/or nephrocalcinosis was 19%–31%, and CKD/kidney failure/renal insufficiency 2.5%–41% (Table). Chronic hypoparathyroidism is a rare disease, which likely contributed to the heterogeneity in reported renal complications in this systematic literature review. Overall, however, patients with chronic hypoparathyroidism who receive conventional therapy had an increased risk of renal complications. Limitations of this systematic literature review are the differences in study design, heterogeneity in imaging methods, which may have affected detection/differentiation of small stones/parenchymal calcinosis, and heterogeneity in the methods of reporting renal outcome data. Additional large-scale studies are needed to understand how the disease pathophysiology and/or conventional treatment may increase the risk of renal complications in patients with chronic hypoparathyroidism.

Funding: Shire, a Takeda company

**Table** Renal complications in patients with chronic hypoparathyroidism.
Article Study Design	Patients, n	Mean ± SD Duration of Disease/Follow-up, years	Methods	Patients with Nephrolithiasis	Patients with Nephrocalcinosis	Patients with CKD/renal insufficiency*
Hadker N, et al. Endocr Pract. 2014;20(7):671–679 Patient self-reporting in a cross-sectional survey	374	Duration: 12.6 ± 12.4	Self-report; CKD reported as chronic kidney failure	35.5%	22% with severe HypoPT vs 6% with mild HypoPT (P ≤ 0.05)	19% with severe HypoPT vs 2.5% with mild HypoPT (P ≤ 0.05)
Meola A, et al. J Endocrinol Invest. 2018;41(10):1221–1226	Prospective study	90	Duration: 9 ± 7 Median (IQR) follow-up: 7.0 (4–11)	Renal ultrasound; CKD: CKD-EPI equation 30%	0	12%
Underbjerg L, et al. J Bone Miner Res. 2013;28(11):2277–2285 Retrospective follow-up study using national health registry data	688	Median (IQR) duration: 8 (4–12) Follow-up: 8.4	Determined by ICD-8 or ICD-10 codes; CKD reported as renal insufficiency	2%	Not reported	5%
Underbjerg L, et al. J Bone Miner Res. 2015;30(9):1738–1744 Retrospective follow-up study using national health registry data	180	Not reported	Determined by ICD-8 or ICD-10 codes; CKD reported as renal insufficiency	1%	Not reported	8%
Arlt W, et al. Eur J Endocrinol. 2002;146(2):215–222 Cross-sectional study	25	Median (range) duration: 3 (0.5–38)	Renal ultrasound	8%	0	Not reported
Lopes MP, et al. Arch Endocrinol Metab. 2016;60(6):532–536 Retrospective observational study	55	Duration: 11.2 ± 7.5 Follow-up: Not reported	Renal ultrasound CKD: Cockcroft-Gault formula CKD stages per KDIGO	Nephrolithiasis and nephrocalcinosis reported combined: 25% (10/40 with imaging)		33% in stage 2 9% in stage 3 2% in stage 4 2% in stage 5
Leidig-Bruckner G, et al. Horm Metab Res. 2016;48(12):806–813 Retrospective, longitudinal chart review	33	Duration: 15.9 ± 9.4 Follow-up: 11.9 ± 6.6	Radiologic imaging (ultrasound, CT, and/or MRI); CKD:Cockcroft-Gault formula	Nephrolithiasis and nephrocalcinosis reported combined: 27% Partial HypoPT: 25% Complete HypoPT: 31%		Partial HypoPT: 5% Complete HypoPT: 23%
Mitchell DM, et al. J Clin Endocrinol Metab. 2012;97(12):4507–4514 Retrospective, longitudinal chart review	120	Duration of disease: 17 ± 16 Follow-up: 7.4 ± 5.1	Renal/abdominal ultrasound and abdominal CT; CKD: MDRD equation	Nephrolithiasis and nephrocalcinosis reported combined: 31% (17/54 with imaging)		41%
Astor MC, et al. J Clin Endocrinol Metab. 2016;101(8):3045–3053 Patient survey using hospital registry	283	Not reported	CKD: MDRD formula	Not reported	Not reported	18%
Underbjerg L, et al. J Bone Miner Res. 2018;33(5):822–831 Case-controlled retrospective study using national health registry data	431	Median (range), duration: 12.7 (0.5–87.1) Follow-up: Not reported	CKD reported as renal insufficiency	Not reported	Not reported	21%
Levy I, et al. J Clin Endocrinol Metab. 2015;100(11):4106–4113 Long-term retrospective follow-up study	29 (paediatric)	Duration: 9.1 ± 5.5 Follow-up: 7.4 ± 5.0	Renal ultrasound; CKD: eGFR (revised Schwartz estimating equation for nonchronic kidney disease populations)	0	38%	0 45% had avg eGFR 60–90 mL/min/1.73 m2
Kim JH, et al. Clin Endocrinol (Oxf). 2015;83(6):790–796 Long-term retrospective	37 (paediatric)	Follow-up: 7.0 ± 5.3	Renal imaging in 26 pts (conducted every ~2.5 y)	Nephrolithiasis and nephrocalcinosis reported combined: 19%		Not reported
Note: One study from the database search did not provide numerical data and is not included in this table (Bohrer T, et al. Eur Surg. 2007;39(1):39–44). *CKD defined as < 60 ml/min/1.73 m2 or <60 ml/min unless otherwise noted. CKD = chronic kidney disease; CKD-EPI = chronic kidney disease epidemiology collaboration; CT = computed tomography; eGFR = estimated glomerular filtration rate; HypoPT = hypoparathyroidism; ICD = International Classification of Diseases; IQR = interquartile range; KDIGO = Kidney Disease Outcomes Quality Initiative; MDRD = modification of diet in renal disease; MRI = magnetic resonance imaging.

Endocrine Abstracts

AEP212