Histologic characterization and risk factors for persistent albuminuria in adolescents in a region of highly prevalent end-stage renal failure of unknown origin.

Background: End-stage renal failure of unknown origin (ESRD-UO) is a public health problem in Mexico and many regions of the world. The prevalence of ESRD-UO in Aguascalientes, Mexico, is one of the highest worldwide, particularly in adults between 20 and 40 years of age. Our aim was to screen adolescents for chronic kidney disease (CKD) to identify risk factors and histologically characterize adolescents with persistent albuminuria. Methods: This was a cross-sectional, observational and comparative study of adolescents in whom serum creatinine and the albumin:creatinine ratio (ACR) were determined when screening for CKD. A clinical evaluation and risk factor survey were conducted. Patients with an abnormal ACR (≥30 mg/g) or a low glomerular filtration rate (GFR) (≤75 mL/min/1.73 m2) were re-evaluated and a renal ultrasound (US) was obtained. A kidney biopsy was performed in patients with persistent albuminuria. Results: A total of 513 students were included; 19 had persistent albuminuria and 494 were controls. The prevalence of persistent albuminuria was 3.7% [95% confidence interval (CI) 2.1-5.3]. Only one patient had a decreased GFR. None of the patients with persistent albuminuria had anatomical abnormalities of the urinary tract by renal US. Patients with persistent albuminuria had a decreased total renal volume compared with the control group (150 versus 195 mL/m2; P < 0.01). Eighteen kidney biopsies were performed; 72% had glomerulomegaly and only one patient had mild fibrosis. Podocyte abnormalities were evident on electron microscopy, including partial fusion (100%), microvillous degeneration (80%) and increased organelles (60%). Risk factors for persistent albuminuria were: homestead proximity to maize crops, the use of pesticides at the father's workplace, a family history of CKD and blood pressure abnormalities. The body mass index and breastfeeding were protective factors. Conclusions: The prevalence of persistent albuminuria in adolescents in Aguascalientes is high and histologic compromise is characterized by podocyte injury in the absence of fibrosis. The renal volume of persistent albuminuria patients was decreased, suggesting oligonephronia. Exposure to environmental toxins such as pesticides, even prenatally, may be responsible for this pathological entity. Screening programs in adolescents by determining ACR are necessary in this setting.

Efficacy and Safety of Ivermectin and Hydroxychloroquine in Patients with Severe COVID-19: A Randomized Controlled Trial.

During the first year of the COVID-19 pandemic, unauthorized drugs were widely used. Ivermectin and hydroxychloroquine are drugs that inhibit viral replication in vitro and that have been used in several medical centers. This clinical trial analyzes their efficacy in hospitalized patients with moderate COVID-19. Methods: This a controlled, clinical, randomized, double-blind trial that included hospitalized patients with COVID-19-induced pneumonia, without severe respiratory failure. Patients were randomized to one of three groups: Group 1-hydroxychloroquine, 400 mg every 12 h on the first day and, subsequently, 200 mg every 12 h for 4 days; Group 2-ivermectin, 12 mg or 18 mg, according to patient weight; and Group 3-placebo. At inclusion, blood samples for arterial blood gases and biochemical markers were obtained. The primary outcome was established as the length of stay due to patient improvement and the rate of respiratory deterioration or death. Results: During the month of August 2020, the admission of patients requiring hospitalization mostly encompassed cases with severe respiratory failure, so we ended the recruitment process and analyzed the data that was available at the time. One hundred and six (106) patients with an average age of 53 yrs (±16.9) were included, with a greater proportion of males (n = 66, 62.2%). Seventy-two percent (72%) (n = 76) had an associated comorbidity. Ninety percent (90%) of patients were discharged due to improvement (n = 96). The average duration of hospitalization was 6 days (IQR, 3-10). No difference in hospitalization duration was found between the treatment groups (Group1: 7 vs. Group 2: 6 vs. Group 3: 5, p = 0.43) nor in respiratory deterioration or death (Group 1: 18% vs. Group 2: 22.2% vs. Group 3: 24.3%, p = 0.83). Conclusions: In non-critical hospitalized patients with COVID-19 pneumonia, neither ivermectin nor hydroxychloroquine decreases the number of in-hospital days, respiratory deterioration, or deaths.

Chronic Kidney Disease Risk Profile in Renal Donors in Aguascalientes, Mexico: A Retrospective Cohort Study.

BACKGROUND: In the last decade, kidney donation has been recognized as a risk factor for end-stage renal disease (ESRD). ESRD risk calculators have been recently perfected in North American populations. In Mexico, the rates of overweight, obesity, and diabetes mellitus (DM) are among the highest worldwide; nevertheless, most kidney transplants are obtained from living donors. This study aims to describe the risk profile for chronic kidney disease (CKD) development in kidney donors in a highly active transplant center in Central Mexico. METHODS: We conducted a retrospective, observational, descriptive cohort study of kidney donors followed at the Hospital Centenario Miguel Hidalgo (CHMH). We used the pretransplant CKD risk calculator at 15 years and over a lifetime (www.transplantmodels.com/esrdrisk). Aside from the calculator of kidney failure risk, we also used the calculator for postdonation CKD risk (www.transplantmodels.com/donesrd/). Factors associated with a glomerular filtration rate (GFR) <60 mL/min were evaluated by univariate and multivariate analysis. RESULTS: The study included 543 donors. The average follow-up period was 1.7 years (±2.7) with a median of 0.7 years (interquartile range, 0.2-2.1). The average predicted risk for ESRD development at 15 years was 0.08% (±0.1); 25.6% had a risk >0.1%, and only 1 patient had a risk >1%. The lifetime ESRD risk was 0.62% (±0.5); 15% had a risk >1%, and the greatest risk was 3.5%. The median of patients at risk of developing postdonation ESRD was 1 in 10,000 donors (0.6-1.5) at 5 years, 5.7 in 10,000 donors (3.5-8.8) at 10 years, 15 in 10,000 donors (9.1-23.2) at 15 years, and 31 in 10,000 donors (18.9-47.7) at 20 years. During the follow-up period, 52 patients developed a GFR of <60 mL/min. Both risk estimation formulas were significantly associated with a GFR of <60 mL/min. Among the individual factors, the GFR (hazard ratio 0.96, 95% confidence interval 0.94-0.97, P < .001) and the urinary albumin to creatinine ratio (hazard ratio 1.009, 95% confidence interval 1.005-1.01, P < .001) remained statistically significant. CONCLUSION: The risk of ESRD in kidney donors in Aguascalientes, Mexico, is similar to that described in the United States. Risk calculators are an indispensable decision-making tool to better understand kidney donors in our milieu.