Incidence and outcomes of kidney replacement therapy for end-stage kidney disease due to primary glomerular disease in Europe: findings from the ERA Registry.

BACKGROUND AND HYPOTHESIS: Primary glomerular disease (PGD) is a major cause of end-stage kidney disease (ESKD) leading to kidney replacement therapy (KRT). We aimed to describe incidence (trends) in individuals starting KRT for ESKD due to PGD and to examine their survival and causes of death. METHODS: We used data from the European Renal Association (ERA) Registry on 69 854 patients who started KRT for ESKD due to PGD between 2000 and 2019. ERA primary renal disease codes were used to define six PGD subgroups. We examined age and sex standardized incidence, trend of the incidence, and survival. RESULTS: The standardized incidence of KRT for ESKD due to PGD was 16.6 per million population (pmp), ranging from 8.6 pmp in Serbia to 20.0 pmp in France. IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) had the highest incidence of 4.6 pmp and 2.6 pmp, respectively. Histologically non-examined PGDs represented over 50% of cases in Serbia, Bosnia and Herzegovina, and Romania and were also common in Greece, Estonia, Belgium, and Sweden. The incidence declined from 18.6 pmp in 2000 to 14.5 pmp in 2013, after which it stabilized. All PGD subgroups had five-year survival probabilities above 50%, with crescentic glomerulonephritis having the highest risk of death (adjusted hazard ratio: 1.8 [95% confidence interval: 1.6-1.9]) compared with IgAN. Cardiovascular disease was the most common cause of death (33.9%). CONCLUSION: The incidence of KRT for ESKD due to PGD showed large differences between countries and was highest and increasing for IgAN and FSGS. Lack of kidney biopsy facilities in some countries may have affected accurate assignment of the cause of ESKD. The recognition of the incidence and outcomes of KRT among different PGD subgroups may contribute to a more individualized patient care approach.

Calcium-mediated parathyroid hormone release changes in patients treated with the calcimimetic agent cinacalcet.

BACKGROUND: The parathyroid-calcium (Ca(2+)-PTH) curve expresses modulation of parathyroid hormone (PTH) secretion by the parathyroid gland as a function of changing extracellular Ca(2+) concentration. Patients with hyperparathyroidism (HPT) show a rightward shift of the curve compared with controls, suggesting a reduced sensitivity of parathyroid cells to Ca(2+). Increasing the sensitivity of the parathyroid gland to extracellular Ca(2+) by manipulation of the Ca(2+)-sensing receptor (CaR) may have therapeutic potential. Calcimimetics allosterically modify CaR and render it more sensitive to extracellular Ca(2+), accounting for the simultaneous reduction of Ca(2+) and PTH seen in most patients. METHODS: The Ca(2+)-PTH curve was evaluated in 10 haemodialysis patients, with baseline intact PTH levels >300 pg/ml in two haemodialysis sessions, one before and the other after (range, 9-22 weeks) cinacalcet treatment. In each session a 2-h low-dialysate Ca(2+) concentration was used to induce hypocalcaemia and maximally stimulate PTH secretion, followed immediately by a 2-h high-dialysate Ca(2+) concentration to induce hypercalcaemia and maximally inhibit PTH secretion. RESULTS: Significant decreases in ionized Ca(2+) and intact PTH were observed following cinacalcet treatment. Cinacalcet treatment also led to a decrease in the set point for Ca(2+) and to a leftward shift of the Ca(2+)-PTH curve. Significant differences were present in all segments of the Ca(2+)-PTH curves. CONCLUSION: The pathological rightward shift of the Ca(2+)-PTH curve seen in many HPT patients may be reversed by cinacalcet treatment.

The renal benefits of a healthy lifestyle.

Over the next decade, the number of patients with end-stage renal disease requiring treatment by dialysis may double, and even developed nations will have difficulty coping with this alarming increase. There is an urgent need to highlight the importance of modifiable risk factors as a basis for treatment strategies to prevent the development and progression of chronic kidney disease (CKD). This should include active extension of our current understanding of a healthy lifestyle.

Parathyroidectomy in dialysis patients.

Subtotal parathyroidectomy or total parathyroidectomy (PTx) with autotransplantation are surgical procedures considered while the patient is included on the waiting list for renal transplantation. Total PTx alone is based in the possibility that a fragment of tissue (nodular hyperplasia in particular) left in the same pathophysiological environment of long term dialysis would show the same behavior and reproduce in time the same clinicopathological picture. The persistence of uremia induces a continued growth stimulus developing residual hyperplasia and consequently a very high risk of recurrence. We performed total PTx alone in 15 uremic patients excluded for renal transplantation 10 patients with undetectable iPTH serum concentration and were followed up for 37 to 144 months. There was no evidence of clinical bone disease (bone pain or fractures). Bone mineral lumbar spine and hip density was measured at the end of follow-up. The z score data showed that all patients had a bone mass similar than that expected for their age. Bone biopsies performed in four patients showed a uniform picture of low turnover without aluminium staining. Calcification of small arteries (digital and arcade vessels in hands and feet) were evaluated pre and post total PTx alone in nine out of the 10 patients with undetectable PTH levels. The small vessel calcification was present in five patients at the moment of PTx. At the end of the long term follow-up only one patient showed progression. In conclusion, total PTx without autotransplantation is a very effective and adequate treatment for refractory severe hyperparathyroidism in patients excluded for renal transplantation. Aluminium related osteopathy post PTx is a risk to be controlled with aluminium "free" dialysis water and avoiding aluminium containing phosphate binders.