Clinical Impact of Hypercalcemia in Kidney Transplant

Abstract

Hypercalcemia (HC) has been variably reported in kidney transplanted (KTx) recipients (5–15%). Calcium levels peak around the 3rd month after KTx and thereafter slightly reduce and stabilize. Though many factors have been claimed to induce HC after KTx, the persistence of posttransplant hyperparathyroidism (PT-HPT) of moderate-severe degree is universally considered the first causal factor. Though not proven, there are experimental and clinical suggestions that HC can adversely affect either the graft (nephrocalcinosis) and other organs or systems (vascular calcifications, erythrocytosis, pancreatitis, etc.). However, there is no conclusive evidence that correction of serum calcium levels might avoid the occurrence of these claimed clinical effects of HC. The best way to reduce the occurrence of HC after KTx is to treat as best we can the secondary hyperparathyroidism (SHP) during the uraemic stages. The indication to Parathyroidectomy (PTX), either before or after KTx, in order to prevent or to treat, respectively, HC after KTx, is still a matter of debate which has been revived by the availability of the calcimimetic cinacalcet for the treatment of PT-HPT. However, we still need to better clarify many points as regards the potential adverse effects related to either PTX or cinacalcet use in this clinical set, and we are waiting for the results of future randomized controlled trials to achieve some more definite conclusions on this topic.

Surgical management of secondary hyperparathyroidism in chronic kidney disease—a consensus report of the European Society of Endocrine Surgeons

“…Renal HPT in CKD can be responsible for several symptoms or organs failures [107], leading to a significant decrease of the life expectancy [105,108]. Three categories of patients with renal HPT can be distinguished: dialysis patients without perspective of renal transplantation; dialysis patients with perspective of renal transplantation and patients with renal transplant.…”

“…Despite better understanding of the pathophysiologic mechanisms of renal HPT and efforts to standardize management of patients with renal HPT [40], controversial opinions regarding different treatment options and their effectiveness prevail [107]. The two main problems are the variations of follow-up 5 of patients suffering from renal HPT either before or after renal transplantation and the management of the treatment with medical and surgical strategies.…”

“…Many published studies do not report the level of vitamin D [109] and use different thresholds to define hypercalcaemia, sometimes using ionized calcium, total calcium levels or corrected calcium levels [107]. Dialysis patients require intensive medical therapy [7] to compensate for hypocalcaemia, hyperphosphoraemia and lack of vitamin D; and nephrologists often hesitate to discuss surgery before a long-standing medical treatment history evolves refractory.…”

“…Serum calcium level of >9.5 mg/dl [106,125] was also a significant risk factor for necessary PTX after transplantation (EL 4) but was less specific than PTH levels (OR=6 for undergoing PTX in case of Ca >9.5 mg/dl 1 year before transplantation [106]). Some authors claim PTH of >800 pg/ml and serum calcium of >10.4 mg/dl despite medical therapy represent an absolute indication for PTX before transplantation due to the high rates of persistent HPT after transplantation in these patients [107] (EL 4).…”

“…Its introduction decreases renal function, which is reversible after cessation, suggesting the same haemodynamic effect like PTX. Some studies observed a regression of parathyroid gland volume on ultrasonography with cinacalcet [132,133] (EL 3), but its effect on urinary calcium excretion is not known and studies reported contradictory results (unchanged, increased or reduced calcium excretion) [107]. Above all, cinacalcet is only approved for treatment of renal HPT and is very expensive [134] (EL 2), rendering PTX as primary effective and longterm option for transplanted patients.…”