Department of Nephrology- Ain Shams University, Cairo, Egypt Effect of total parathyroidectomy with and without autoimplantation in prevalent hemodialysis patients Department of Nephrology- Ain Shams University, Cairo, Egypt Sahar Shawky Amr Mohab Haitham Ezzat

Secondary hyperparathyroidism (SHPT) is common in chronic kidney disease. Despite the initiation of new therapeutic agents, several patients will require parathyroidectomy (PTX). There are three options for the surgical treatment of SHPT: subtotal PTX , total PTX with autotransplantation (TPTX+AT), and total PTX without autotransplantation (TPTX). APSN 15 ; 441–447, 2009.

Aim of the study The aim of the present study was to compare total parathyroidectomy with autotransplantation (TPTX + AT) versus total parathyroidectomy without autotransplantation (TPTX) for secondary hyperparathyroidism in prevalent hemodialysis patients with respect to long-term outcomes.

Patients and methods This is a retrospective study which included 40 ESRD patients on regular HDx thrice weekly (18 men and 22 women) who underwent parathyroidectomy (PTX); with secondary hyperparathyroidism and PTH was above 800 pg/ml after failure of medical treatment (alfacalcidol and cinacalcet) for at least 6 months. (Group I) 20 patients underwent total (PTX) with autoimplantation (median age 49 years; range 24 - 60 years; median dialysis duration before PTX :9 years; range 5–15 years) . (Group II) 20 patients underwent total (PTX) without autoimplantation (median age 46 years; range 25 - 64 years; median dialysis duration before PTX :6 years; range 2–13 years).

Preoperative Stage:. All patients had the following laboratory tests: iPTH, Serum Calcium, phosphorus, albumin, Alkaline Phosphatase, CBC. Lumbosacral plain x-ray.

Operative stage: Postoperative stage: All patients underwent surgery in the form of bilateral neck exploration with total parathyroidectomy without autoimplantation or total parathyroidectomy with autoimplantation of half of a gland in sternocleidomastoid or forearm. Postoperative stage: All patient had oral tablets, containing Calcium Carbonate, active Vitamin D (alphacalcidol) 1ug once daily. All patients had postoperative iPTH assessment, daily serum Ca assessment till discharge. (IV) Calcium Gluconate was administered in cases of symptomatic hypocalcaemia, or asymptomatic severe hypocalcaemia defined as serum Calcium below 6 mg/dl. The presence of bony symptoms at the most recent clinic appointment was recorded using a verbal scale consisting of four options (resolved, improved, unchanged, or unknown).

No statistically significant difference between the two groups regarding gender and age Results Age (years) Groups T-Test Group I Group II P-value Range 24.000 - 60.000 25.000 64.000 0.246 Mean ±SD 49.350 ± 8.343 46.095 9.300 Gender Groups Chi- Square Group I (NO= 20) Group II (NO=20) Total (NO= 40) N % P- value Female 11 55.00 22 1.000 Male 9 45.00 18 Total 20 100.00 40

Duration of dialysis (years) There was a highly statistically significant difference between both groups regarding dialysis duration Duration of dialysis (years) Groups T-Test Group I Group II P-value Range 5.000 - 15.000 2.000 13.000 0.006* Mean ±SD 9.550 ± 3.395 6.714 2.831

Comparison between the two studied groups according to bone aches Chi-Square Group I Group II Total N % P-value Resolved 2 10.00 3 15.00 5 12.50 0.820 Improved 11 55.00 12 60.00 23 57.50 Unchanged. 4 20.00 6 Unknown 20 100.00 40

Corrected Ca (mg/dl) Pre Post There was a statistically significant difference between the two groups according to postoperative s.Ca (p = 0.016), while there was no statistically significant difference between the two groups according to pre-operative s.Ca   Corrected Ca (mg/dl) Difference Paired T-test Pre Post Mean SD P-value Group I Range 8.5 - 11.5 6.5 2.145 1.178 <0.001* Mean±SD 9.800 ± 0.953 7.655 0.526 Group II 11.6 5.8 8.3 2.620 0.631 9.770 0.971 7.150 0.723 0.922 0.016*

Duration of s.Ca normalization (days) There was a statistically significant difference between the two groups according to duration of Ca normalization Groups Duration of s.Ca normalization (days) Mann- Whitney Test Range Median Interquartile Range Mean Rank P-value Group I 5.000 - 30.000 12.000 6.000 17.100 0.041* Group II 7.000 60.000 14.000 13.000 24.714

Phosphorus (mg/dl) Pre Post In case of comparison between pre-operative and post-operative phosphorus level in both groups there are no statistically significant difference between them (p = 0.165) and (p = 0.219) respectively. There is also highly statistically significant difference when comparing pre-operative and postoperative phosphorus levels throughout both groups (p = <0.001 in both of them)   Phosphorus (mg/dl) Difference Paired T-test Pre Post Mean SD P- value Group I Range 5.20 - 9.60 3.90 5.80 1.985 0.66 4 <0.001 * Mean±S D 6.69 ± 1.09 4.71 0.56 Group II 3.50 10.4 0 3.30 6.50 2.405 1.19 4 7.41 1.97 5.00 0.89 T-test P-value 0.165 0.219

There was no statistically significant difference between the two groups regarding ALP ALP(U/L) Groups T-Test Group I Group II P-value Range 290.000 - 1345.000 193.000 1500.000 0.168 Mean ±SD 668.550 ± 282.362 795.619 295.492

There is no statistically significant difference when comparing the plain x-ray spine throughout both groups (p = 0.427).

Pre-operative PTH :There was highly statistically significant difference between the two groups according to iPTH levels 21 20 N = Group II Group I PTH level (pg/ml) 4000 3000 2000 1000 Groups iPTH level (pg/ml) Mann- Whitney Test Range Median Interquartil e Range Mean Rank P-value Group I 1135.000 - 2850.000 1709.000 744.250 14.650 0.001* Group II 1447.000 3429.000 2401.000 650.000 27.048

Follow up of iPTH till a year after parathyroidectomy in group I: Comparison of pre-operative iPTH values with the Post operative iPTH, iPTH after 1 month, iPTH after 3 months, iPTH after 6 months and iPTH after 1 year showed a highly statistical significance (p = <0.001) iPTH level  Group I Friedman Test Range Median Interquartile Range Mean Rank X2 P-value iPTH level (pg/l) 1135.000 - 2850.000 1709.000 744.250 6 46.28 <0.001* Post operative 8.500 551.000 87.500 101.250 2.35 After 1 month 11.000 561.000 165.750 2.95 After 3 months 10.000 570.000 85.500 213.750 3.3 After 6 months 12.400 564.000 84.500 278.250 3.25 After 1 year 14.000 542.000 79.000 243.550 3.15

Follow up of iPTH till a year after parathyroidectomy in group II comparison of pre-operative iPTH with the Post operative iPTH, iPTH after 1 month, iPTH after 3 months, iPTH after 6 months and iPTH after 1 year showed a highly statistical significance (p = <0.001) iPTH level  Group II Friedman Test Range Median Interquartile Range Mean Rank X2 P-value iPTH level (pg/l) 1447.000 - 3429.000 2401.000 650.000 6 80.34 <0.001 Post operative 3.000 40.500 8.500 10.650 1.55 After 1 month 48.000 12.400 8.450 2.1 After 3 month 4.200 45.300 13.600 13.650 2.85 After 6 month 4.600 87.000 16.400 31.650 3.75 After 1 year 122.000 24.000 57.300 4.75

Within group II, nine patients (45%) had measurable post-operative iPTH levels within the normal range, and 11 patients (55%) actually had iPTH levels below the normal range. At the end of the follow-up time (12 months), we saw recurrent sHPT, in 4 patients (20%) . In group I, 5 patients (25%) had measurable post-operative iPTH levels within the normal range, and 10 patients (50%) had iPTH levels above the upper limit of the normal range thus this is could be considered Persistent sHPT but 4 patients only (20%) showed rise of the PTH levels after 6 months of follow up (recurrence). 1 patient had iPTH level below the normal range.

Conclusion Total parathyroidectomy with autotransplantation, and total parathyroidectomy without implantation produced similar results when considering the regression of osteodystrophy symptoms e.g bone aches. As one could anticipate, group II showed increased incidence of hypoparathyroidism (11 patients, 55%) while group I showed persistence (9 patients 45% ) and recurrence (4 patients, 20% ).

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