Long-term effects of hypercalcemia in kidney transplant recipients with persistent hyperparathyroidism.

BACKGROUND: Hypercalcemia is highly prevalent in kidney transplant recipients with hyperparathyroidism. However, its long-term impact on graft function is uncertain. METHODS: We conducted a prospective cohort study investigating adverse graft outcomes associated with persistent hypercalcemia (free calcium > 5.2 mg/dL in ≥ 80% of measures) and inappropriately elevated intact parathyroid hormone (> 30 pg/mL) in kidney transplant recipients. Asymptomatic mild hypercalcemia was monitored unless complications developed. RESULTS: We included 385 kidney transplant recipients. During a 4-year (range 1-9) median follow-up time, 62% of kidney transplant recipients presented persistent hypercalcemia. Compared to kidney transplant recipients without hypercalcemia, there were no significant differences in graft dysfunction (10% vs. 12%, p = 0.61), symptomatic urolithiasis (5% vs. 3%, p = 0.43), biopsy-proven calcium deposits (6% vs. 5%, p = 1.0), fractures (6% vs. 4%, p = 0.64), and a composite outcome of urolithiasis, calcium deposits, fractures, and parathyroidectomy indication (16% vs. 13%, p = 0.55). In a subset of 76 kidney transplant recipients, subjects with persistent hypercalcemia had higher urinary calcium (median 84 [43-170] vs. 38 [24-64] mg/day, p = 0.03) and intact fibroblast growth factor 23 (median 36 [24-54] vs. 27 [19-40] pg/mL, p = 0.04), and lower 25-hydroxyvitamin D levels (11.3 ± 1.2 vs. 16.3 ± 1.4 ng/mL, p < 0.001). In multivariate analysis, pretransplant intact parathyroid hormone < 300 pg/mL was associated with a reduced risk of post-transplant hypercalcemia (OR 0.51, 95% CI 0.32-0.80). CONCLUSIONS: Long-term persistent mild hypercalcemia (tertiary hyperparathyroidism) was frequent in kidney transplant recipients in our series. This condition presented with lower phosphate and 25-hydroxyvitamin D, and higher urinary calcium and intact fibroblast growth factor 23 levels compared to kidney transplant recipients without hypercalcemia, resembling a mild form of primary hyperparathyroidism. Despite these metabolic derangements, the risk of adverse graft outcomes was low.

A modified renal angina index in critically ill patients with COVID-19.

BACKGROUND: The renal angina index (RAI) is a tool that has been validated by several studies in the pediatric population to predict the development of severe acute kidney injury (AKI). The aims of this study were to evaluate the efficacy of the RAI in predicting severe AKI in critically ill patients with COVID-19 and to propose a modified RAI (mRAI) for this population. METHODS: This was a prospective cohort analysis of all COVID-19 patients receiving invasive mechanical ventilation (IMV) who were admitted to the intensive care unit (ICU) of a third-level hospital in Mexico City from 03/2020 to 01/2021. AKI was defined according to KDIGO guidelines. The RAI score was calculated for all enrolled patients using the method of Matsuura. Since all patients had the highest score for the condition (due to receiving IMV), the score corresponded to the delta creatinine (ΔSCr) value. The main outcome was severe AKI (stage 2 or 3) at 24 and 72 h after ICU admission. A logistic regression analysis was applied to search for factors associated with the development of severe AKI, and the data were applied to develop a mRAI and compare it vis-à-vis the efficacy of both scores (RAI and mRAI). RESULTS: Of the 452 patients studied, 30% developed severe AKI. The original RAI score was associated with AUCs of 0.67 and 0.73 at 24 h and 72 h, respectively, with a cutoff of 10 points to predict severe AKI. In the multivariate analysis adjusted for age and sex, a BMI ≥30 kg/m2, a SOFA score ≥6, and Charlson score were identified as risk factors for the development of severe AKI. In the new proposed score (mRAI), the conditions were summed and multiplied by the ΔSCr value. With these modifications, the AUC improved to 0.72 and 0.75 at 24 h and 72 h, respectively, with a cutoff of 8 points. CONCLUSIONS: The original RAI is a limited tool for patients with critical COVID-19 receiving IMV. The mRAI, with the parameters proposed in the present study, improves predictive performance and risk stratification in critically ill patients receiving IMV.

Community- and Hospital-Acquired Acute Kidney Injury in COVID-19: Different Phenotypes and Dismal Prognosis.

INTRODUCTION: Acute kidney injury (AKI) is common in coronavirus disease 2019 (COVID-19). It is unknown if hospital-acquired AKI (HA-AKI) and community-acquired AKI (CA-AKI) convey a distinct prognosis. METHODS: The study aim was to evaluate the incidence and risk factors associated with both CA-AKI and HA-AKI. Consecutive patients hospitalized at a reference center for COVID-19 were included in this prospective cohort study. RESULTS: We registered 349 (30%) AKI episodes in 1,170 hospitalized patients, 224 (19%) corresponded to CA-AKI, and 125 (11%) to HA-AKI. Compared to patients with HA-AKI, subjects with CA-AKI were older (61 years [IQR 49-70] vs. 50 years [IQR 43-61]), had more comorbidities (hypertension [44 vs. 26%], CKD [10 vs. 3%]), higher Charlson Comorbidity Index (2 points [IQR 1-4] vs. 1 point [IQR 0-2]), and presented to the emergency department with more severe disease. Mortality rates were not different between CA-AKI and HA-AKI (119 [53%] vs. 63 [50%], p = 0.66). In multivariate analysis, CA-AKI was strongly associated to a history of CKD (OR 4.17, 95% CI 1.53-11.3), hypertension (OR 1.55, 95% CI 1.01-2.36), Charlson Comorbidity Index (OR 1.16, 95% CI 1.02-1.32), and SOFA score (OR 2.19, 95% CI 1.87-2.57). HA-AKI was associated with the requirement for mechanical ventilation (OR 68.2, 95% CI 37.1-126), elevated troponin I (OR 1.95, 95% CI 1.01-3.83), and glucose levels at admission (OR 1.05, 95% CI 1.02-1.08). DISCUSSION/CONCLUSIONS: CA-AKI and HA-AKI portend an adverse prognosis in CO-VID-19. Nevertheless, CA-AKI was associated with a higher comorbidity burden (including CKD and hypertension), while HA-AKI occurred in younger patients by the time severe multiorgan disease developed.

Pirfenidone prevents acute kidney injury in the rat.

BACKGROUND: Pirfenidone is an orally active drug used for the treatment of idiopathic pulmonary fibrosis to slow loss of lung function; it acts mainly through an antifibrotic effect but also possesses antioxidant and anti-inflammatory properties. We assessed the effect of prophylactic administration of pirfenidone on acute kidney injury due to bilateral renal ischemia. METHODS: Eighteen rats were included and divided in: 1) sham-operated rats (S), 2) rats underwent bilateral renal ischemia for 20 min (I/R), and 3) rats treated with pirfenidone 700 mg/kg/day 24 h before surgery and subjected to bilateral renal ischemia for 20 min (I/R + PFN). All the rats were euthanized and studied 24 h after renal reperfusion. RESULTS: As was expected, the I/R group exhibited a significant reduction in creatinine clearance, urinary output and renal blood flow, as well as extensive tubular injury. These alterations were associated with a significant decrease in urinary excretion of nitrites and nitrates (UNO2/NO3V). In the I/R + PFN group, recovery of renal function and UNO2/NO3V was observed, together with lesser histological signs of tubular injury compared to the I/R group. CONCLUSIONS: This study shows that prophylactic administration of pirfenidone prevented acute kidney injury due to bilateral ischemia in the rat. Recovery of NO production appears to be one of the mechanism of pirfenidone renoprotective effect. Our findings suggest that pirfenidone is a promising drug to reduce renal injury induced by I/R.