Hypercalcemia in the nephrology department patients - incidence, etiology and impact on renal function.

Hypercalcemia (HCM) is predominantly caused by primary hyperparathyroidism (PHPT) or malignancy. It's incidence varies from 0.17% to 4.74%. Its numerous manifestations include renal symptoms. AIM: The aim of the study was to assess the incidence and etiology of hypercalcemia in patients hospitalized at the Department of Nephrology of the Warsaw Military Institute, as well as to evaluate its impact on renal function. MATERIALS AND METHODS: In this cross-sectional study patients admitted to the Nephrology Department of the Warsaw Military Institute between January 2017 and December 2018 were retrospectively screened for presence of HCM, defined as total calcium level or corrected calcium level in case of hypoalbuminemia >10.2 mg/dl, measured at least twice. Each patient's medical history as well as other laboratory findings were subsequently analyzed in order to establish the etiology of hypercalcemia. RESULTS: Among 3062 hospitalisations (1993 patients) at The Department, 96 patients had elevated calcium level of which 36 were identified as hypercalcemic (1,81%). Median calcium level was 11.9 mg/dl (IQR: 11.25-13.46) with 22.24 mg/dl being the maximum observed value. Malignancy and drugs having hypercalcemizing effect were the most common etiologies identified, both being found in 9 cases (25%). Other causes of HCM included sarcoidosis, multiple myeloma (analyzed separately from other malignancies), PHPT and hypercalcemic hypocalciuria. In 7 cases HCM etiology could not be established, it therefore remained idiopathic. Acute kidney injury (AKI) developed in 20 patients (56%), in this group serum calcium levels were significantly higher than in non-AKI patients (median: 12.85 mg/dl (IQR:11.82-14.65) vs 11.25 mg/dl (IQR:10.75-11.93); p=0.0039). Additionally, chronic kidney disease (CKD) patients presented significantly lower calcium values than non-CKD patients (median: 11.47 mg/dl (IQR: 10.8-12.6) vs 13.01 mg/dl (IQR:11.9-16.08; p=0.0131). CONCLUSIONS: Hypercalcemia is a rare disorder among Nephrology Department patients, which primary etiology is malignancy and medications having hypercalcemizing effect. Kidney injury is dependent on the severity of hypercalcemia.

Research progress of role of NLRP3 inflammasome in lupus nephritis / 中国免疫学杂志

Systemic lupus erythematosus (SLE)is an autoimmune disease whose pathogenesis is extremely complicated.With the further research,the role of inflammasome in the pathogenesis of Lupus nephritis has also been gradually emphasized.Among them,the nucleotide-binding oligomerization domain-like receptors family pyrin domain containing 3 (NLRP3) inflammasome is the most exhaustive inflammasome.We summarize the related studies on the role of NLRP3 inflammasome in Lupus nephritis in recent years.We found that NLRP3 inflammasome not only plays an important role in the pathogenesis of Lupus nephritis,but also participates in the process of kidney injury by circulating immune cells and renal innate cells.Finally,we introduced two specific inhibitors of NLRP3 inflammasome,β-hydroxybutyrate and MCC950,which provided a new strategy for the treatment of Lupus nephritis.

NLRP3 inflammasome activation regulated by NF-κB and DAPK contributed to paraquat-induced acute kidney injury.

Paraquat can result in dysfunction of multiple organs after ingestion in human. However, the mechanisms of nucleotide-binding domain and leucine-rich repeat containing protein 3 (NLRP3) inflammasome activation in acute kidney injury have not been clearly demonstrated. The aim of this study was to determine the effect of NLRP3 inflammasome activation and its regulation by nuclear factor-kappa B (NF-κB) and death-associated protein kinase (DAPK). Male Wistar rats were treated with intraperitoneal injection of paraquat at 20 mg/kg, and NF-κB inhibitor BAY 11-7082 was pretreated at 10 mg/kg 1 h before paraquat exposure. Additionally, rat renal tubular epithelial cells (NRK-52E) were transfected with small interfering RNA (siRNA) against DAPK to evaluate its role in NLRP3 inflammasome activation. DAPK and NLRP3 inflammasome were evaluated by immunohistochemistry staining or Western blot; the pro-inflammatory cytokines including tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-18 (IL-18) were measured via ELISA. The results showed that NF-κB, DAPK, and NLRP3 inflammasome were activated in paraquat (PQ)-treated rat kidney; the secretion of pro-inflammatory cytokines was significantly increased. These toxic effects were attenuated by NF-κB inhibitor. Besides, the activation of NLRP3 inflammasome and secretion of IL-1ß and IL-18 in paraquat-treated rat renal tubular epithelial cells were inhibited by siRNA against DAPK. In conclusion, NLRP3 inflammasome activation regulated by NF-κB and DAPK played an important role in paraquat-induced acute kidney injury.