Pediatric kidney dimensions and risk of persistent albuminuria in Mexican adolescents.

In Mexico, chronic kidney disease of unknown origin is highly prevalent. Screening studies in adolescents have shown persistent microalbuminuria (pACR), adaptive podocytopathy and decreased kidney volume (KV). Here, we sought to develop normality tables of kidney dimensions by ultrasound in the Mexican state of Aguascalientes pediatric population (0 to 18y) and evaluate the relationship between the KV and pACR among the region's adolescents in a cross-sectional study. Kidney length (KL) and KV were determined by ultrasound. Our findings were compared with those in international literature of different populations where tables and graphs of normal kidney dimensions by ultrasound were reported. We compared organ dimensions in individuals above the age of 11 without albuminuria with those in patients with pACR recruited through screening studies in adolescents in Aguascalientes. This included 1068 individuals to construct percentile tables and graphs of the KL. Kidney dimensions were significantly lower when compared with all international comparisons. From a total 14,805 screen individuals, we compared 218 adolescents with pACR and 377 individuals without significant albuminuria. The Total KV adjusted to body surface (TKVBS) was significantly associated with pACR (odds ratio 1.03, 95% confidence interval 1.02-1.03). The upper quartile of TKVBS was highly associated with pACR (7.57, 4.13-13.87), hypertension (2.53, 1.66-3.86), and hyperfiltration (26 vs 11.5%). Thus, TKVBS is directly associated with pACR while greater KV, arterial hypertension, and hyperfiltration in patients with pACR suggest that the increase in volume is secondary to kidney hypertrophy. Additionally, the adaptative podocytopathy with low fibrosis seen on kidney biopsy which was performed in a subset of patients, and the smaller kidney dimensions in our population point to prenatal oligonephronia as the primary cause of the detected kidney disease.

Changes in the commercial brand of tacrolimus lead to subtherapeutic trough levels and acute rejection in renal transplant recipients.

BACKGROUND: The vigilance of tacrolimus (TAC) trough levels is an essential part of renal transplant follow up. Reduced TAC trough levels and high variability are related to adverse outcomes. The aim of this study was to evaluate the impact of brand changes on tacrolimus (TAC) subtherapeutic (SubT) trough levels, acute rejection (AR), and kidney function. METHODS: This is a prospective, observational cohort study of renal transplant recipients, between January 2016 and October 2018. Tacrolimus trough levels and brand used by the patient were both registered at every consult. Tacrolimus values ≤3.5 ng/mL were considered SubT. RESULTS: 445 patients were included. The median number of TAC brand changes was 2 (IQR, 1-4). Patients were grouped according to the number of brand changes: Group 1 = 0 (n = 107), Group 2 = 1-4 (n = 236), and Group 3 = ≥5 (n = 102). Patients with the greatest number of brand changes had a greater proportion and number of SubT TAC trough levels (Group 1 = 36.4%, average 0.53; Group 2 = 39.8%, average 0.65, Group 3 = 59.8%, average 1.17, P < .001) and AR (Group 1 = 0.9%, Group 2 = 11%, Group 3 = 14.7%, P < .001). On multivariate analysis, SubT levels and the number of brand changes were related to AR. CONCLUSIONS: In Mexico, changes in TAC brand are associated with an elevated frequency of SubT levels. Brand changes and SubT levels are independently associated with acute rejection. The supply policies on TAC brands in Mexico require revision to avoid changing brands as much as possible.

Pre-transplant angiotensin II type 1receptor antibodies: a risk factor for decreased kidney graft function in the early post-transplant period?

Angiotensin II type 1 receptor antibodies (AT1Rab) are associated to a significantly lower graft survival and a higher risk of acute rejection after kidney transplantation. This study aimed to evaluate graft function and BPAR during the 1st year post-transplant (PT) in adult kidney transplant recipients (KTR), between 03/2009 and 08/2012. Pre-KT sera were screened for AT1Rab (ELISA) and HLA-DSA (Luminex). Three groups were analyzed: AT1Rab only (n = 13); HLA-DSA only (n = 8); and no AT1Rab or HLA-DSA (n = 90). No differences were observed in clinical characteristics across groups. A higher percentage of BPAR was observed in the AT1Rab positive group, but this difference was not significant. KTR with AT1Rab had a lower mean eGFR (20 mL/min/1.73m2) when compared to KTR with no Abs at 12 months. The significant difference in eGFR was observed since the 1st month PT. Multivariate analysis showed 4 factors independently and significantly associated with eGFR at 12mos PT: BPAR (-18.7 95%, CI -28.2 to -9.26, p<0.001), AT1Rab (-10.51, CI -20.9 to -0.095, p = 0.048), donor age (-0.42, CI -0.75 to -0.103 p = 0.010), and recipient age (-0.36, CI -0.67 to -0.048, p = 0.024). In this study AT1Rab in pre-transplant sera from KTR, was an independent and significant risk factor contributing to a lower eGFR 12 months. PT. This finding deserves to be confirmed in a larger KTR population.

Biofilm Formation by Escherichia coli Isolated from Urinary Tract Infections from Aguascalientes, Mexico.

Uropathogenic Escherichia coli (UPEC) strains are among the leading causes of urinary tract infections (UTIs) worldwide. They can colonize the urinary tract and form biofilms that allow bacteria to survive and persist, causing relapses of infections and life-threatening sequelae. Here, we analyzed biofilm production, antimicrobial susceptibility, virulence factors, and phylogenetic groups in 74 E. coli isolated from diagnosed patients with UTIs to describe their microbiological features and ascertain their relationship with biofilm capabilities. High levels of ceftazidime resistance are present in hospital-acquired UTIs. Isolates of multidrug resistance strains (p = 0.0017) and the yfcV gene (p = 0.0193) were higher in male patients. All the strains tested were able to form biofilms. Significant differences were found among higher optical densities (ODs) and antibiotic resistance to cefazolin (p = 0.0395), ceftazidime (p = 0.0302), and cefepime (p = 0.0420). Overall, the presence of fimH and papC coincided with strong biofilm formation by UPEC. Type 1 fimbriae (p = 0.0349), curli (p = 0.0477), and cellulose (p = 0.0253) production was significantly higher among strong biofilm formation. Our results indicated that high antibiotic resistance may be related to male infections as well as strong and moderate biofilm production. The ability of E. coli strains to produce biofilm is important for controlling urinary tract infections.

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.

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.

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.

High prevalence of end-stage renal disease of unknown origin in Aguascalientes Mexico: role of the registry of chronic kidney disease and renal biopsy in its approach and future directions.

BACKGROUND: Chronic kidney disease (CKD) is one of the pathologies with the greatest impact on the public health system. Over the last few decades, the relevance of CKD in Mexico has increased, with associated overwhelming costs for care of renal disease. There are no reliable CKD statistics in Mexico. METHODOLOGY: In June 2018, the government of Aguascalientes called on all Health Institutions to create a state registry of treated end-stage renal disease (ESRD). In the same system, a renal biopsy result registry included all the native kidney biopsies obtained in the state of Aguascalientes since 2012. We herein describe the prevalence, incidence and characteristics of the patients included in the CKD and renal biopsy registry in the state of Aguascalientes. RESULTS: As of April 2020, the state has documented 2827 patients on renal replacement therapy (RRT), 1877 on dialysis and 950 that have been transplanted. The prevalence of patients on dialysis is 1326 per million population (p.m.p.), and if transplanted individuals are included, it is 1997 p.m.p. The incidence of treated ESRD in 2019 was 336 p.m.p. (n = 474) in individuals with an average age of 45.6 years (standard deviation ±18), and in a higher proportion of men (61%). There is a bimodal distribution of the age at which RRT was initiated. The first and the most significant peaks are between the ages of 20 and 40 years and are usually the result of CKD of unknown cause (73%). The second peak is between 50 and 70 years of age, and CKD is usually the result of diabetes mellitus and systemic arterial hypertension (59.6%). Since January 2012, 423 biopsies have been recorded. The patient's ages were between 20 and 30 years (n = 112), and the most frequent diagnosis was focal segmental glomerulosclerosis (FSGS) (54%). CONCLUSIONS: The prevalence of treated ESRD in the state of Aguascalientes is high. The disease mostly afflicts young people between 20 and 40 years of age, and there is a clear male predominance. In this age group, the main clinical diagnosis is CKD of unknown origin, and the most frequent biopsy diagnosis was FSGS.

Tacrolimus Trough Levels as a Risk Factor for Acute Rejection in Renal Transplant Patients.

BACKGROUND: Use of tacrolimus (TAC) is pivotal to renal transplant (RT) immunosuppressive maintenance regimens. The aim of this study was to evaluate the relationship between TAC trough levels and the development of acute rejection (AR). MATERIAL AND METHODS: This was a retrospective cohort study. We included recipients transplanted between 01/2008 and 05/2012. Regression analyses (Cox's proportional hazards model) and sub-analysis of AR and TAC levels over different time periods were performed. RESULTS: We included 198 patients with an average age of 32 years (±12.1) and predominantly male (54.5%). Mean follow-up was 2 years (min-max 15d - 5.2yrs). Sixty-two AR events were documented (BL: 31, Cellular AR: 19, Humoral AR: 12). We found that TAC levels (HR 0.76, 0.65-0.88, p<0.001), a high risk for CMV infection (D+/R-) (HR 2.92, 1.47-1.014, p=0.002), pre-transplant donor-specific HLA antibodies (DSA) (HR 3.04 1.29-7.16, p=0.011), and post-RT DSA (HR 2.4, 1.16-4.9, p=0.018) were significantly associated with AR. The relationship between TAC levels and rejection was independent of follow-up duration. CONCLUSIONS: In this analysis, TAC though levels were directly related to AR events; trough levels >8 ng/ml were the most effective in decreasing immunological adverse events. A decrease in TAC levels throughout the post-transplant follow-up period should be considered due to its possible association with AR events.

Comparison of Lupus Nephritis Induction Treatments in a Hispanic Population: A Single-center Cohort Analysis.

OBJECTIVE: To evaluate response rates in an adult lupus nephritis (LN) cohort in Mexico City, Mexico. METHODS: We analyzed 165 patients with biopsy-proven LN histological International Society of Nephrology/Renal Pathology Society classes III, IV, or V, distributed by treatment drug in 3 groups: mycophenolate mofetil (MMF; dosage > 2 g/day per 6 mos, n = 63), intravenous cyclophosphamide (IVC; 0.7 g/m(2) body surface area monthly per 6 pulses, n = 66), or azathioprine (AZA; dosage > 1.5 mg/kg/day per 6 mos, n = 36). Median followup was 31 ± 18 months. The primary endpoint was the proportion of patients achieving complete renal response (CR). Secondary endpoints included the proportion of patients achieving renal response (complete or partial), renal flare-free survival, doubling of serum creatinine, and progression to endstage renal disease (ESRD). RESULTS: MMF induction was superior to IVC (HR 2.00, 95% CI 1.23-3.25, p = 0.005) and AZA (HR 2.12, 95% CI 1.23-3.66, p = 0.007) in the primary endpoint. Censored CR rates at 6, 12, 24, and 36 months were 32.6%, 56.1%, 76.6%, and 94.1% for MMF; 24.2%, 34.4%, 57.9%, and 62.1% for IVC; and 8.4%, 39.8%, 49.7%, and 49.7% for AZA. MMF was also superior in renal response to treatment and renal flare-free survival outcomes. There were no differences between groups in doubling of serum creatinine or progression to ESRD. The induction treatment with MMF (HR 2.04, 95% CI 1.25-3.33, p = 0.005) and absence of vascular lesions on renal biopsy (HR 2.05, 95% CI 1.25-3.37, p = 0.004) were associated with CR, whereas proteinuria at the time of presentation was negatively associated with CR (HR 0.91, 95% CI 0.84-0.98, p = 0.013). CONCLUSION: MMF induction therapy is superior to IVC and AZA in patients with LN of Mexican-mestizo race.

Pre-transplant angiotensin II type 1 receptor antibodies: A risk factor for decreased kidney graft function in the early post-transplant period?

Angiotensin II type 1 receptor antibodies (AT,Rab) are associated with a significantly lower graft survival and a higher risk of acute rejection after kidney transplantation. This study aimed to evaluate graft function and biopsy proven acute rejection (BPAR) during the first year post-transplant in adult renal transplant recipients (RTR), between 03/2009 and 08/2012. Pre-transplant sera were screened for AT1Rab (via enzyme linked immunosorbent assay) and donor specific anti-human leukocyte antigen antibodies (HLA-DSA, via Luminex). Three groups were analyzed: AT1Rab only (n=13); HLA-DSA only (n=8); and no AT1Rab or HLA-DSA (n=90). No differences were observed in clinical characteristics across groups. A higher percentage of BPAR was observed in the AT1Rab positive group, but this difference was not significant. RTR with AT1Rab had a lower median estimated glomerular filtration rate (eGFR=20 ml/min/1.73m2) when compared to RTR with no antibodies at 12 months. A significant difference in eGFR was observed since the first month post-transplant. Multivariate analysis showed four factors independently and significantly associated with eGFR at 12 months post-transplant: BPAR (beta -18.7, 95% CI -28.2 to -9.26, p<0.001), AT,Rab (beta -10.51, 95% CI -20.9 to -0.095 p=0.048), donor age (beta -0.42, 95% CI -0.75 to -0.103, p=0.010), and recipient age (3 -0.36, 95% CI -0.67 to -0.048, p= 0.024). In this study, AT1Rab in pre-transplant sera from RTR was an independent and significant risk factor contributing to a lower eGFR at 12 months posttransplant. This finding deserves to be confirmed in a larger RTR population.

Pre-nephrectomy angiotensin II type 1 receptor antibodies in living kidney donors: A concern?

Angiotensin II type 1 receptor (AT1R) autoantibodies (AT1Rab) have been associated with pre-eclampsia and malignant hypertension. Overactivity of the angiotensin-II/AT1R complex has also been implicated in cardiac, renal, and vascular remodeling, leading to mortality and morbidity from cardiovascular disease. Pre-donation prevalence and possible post-donation effects of AT1Rab in living kidney donors (LKD) are unknown. In this study, sera obtained the day before nephrectomy and kept frozen at -70 degrees C from 113 strictly normotensive and non-obese LKD were tested for AT1Rab by OneLambda detection assay. AT1Rab titers >or=17 international units were considered positive. Pre-donation renal function [estimated glomerular filtration rate (eGFR)] and blood pressure at 1 and 12 months post-donation were recorded in every patient. Ten of 113 (8.8%) LKD yielded a positive AT1Rab result. History of sensitization events was similar in both groups. There was no difference in renal function between LKD with positive and negative AT1Rab results, 1 (mean eGFR 73.8 versus 72.4 mL/min/1.73m2) and 12 months post-donation (mean eGFR 74.1 versus 74.5 mL/min/1.73m2). During follow-up, none of the LKD developed hypertension (defined as blood pressure >130/85), nor did they require antihypertensive drugs. AT1Rab are apparently indolent in healthy adults after short-term follow-up. Longer observation of all LKD will be necessary to draw final conclusions.