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.

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.

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.

Osteocalcin serum concentrations and markers of energetic metabolism in pediatric patients. Systematic review and metanalysis.

Background: Osteocalcin plays a role in glucose metabolism in mice, but its relevance in human energetic metabolism is controversial. Its relationship with markers of energetic metabolism in the pediatric population has not been systematically addressed in infants and adolescents. Objective: This study aims to assess the mean differences between tOC, ucOC, and cOC among healthy children and children with type 1 or type 2 diabetes (T1D or T2D) and the correlation of these bone molecules with metabolic markers. Methods: A systematic review and metanalysis were performed following PRISMA criteria to identify relevant observational studies published in English and Spanish using PubMed, Scopus, EBSCO, and Web of Science databases. The risk of bias was assessed using New Castle-Ottawa scale. Effect size measures comprised standardized mean difference (SMD) and Pearson correlations. Heterogeneity and meta-regressions were performed. Results: The 20 studies included were of high quality and comprised 3,000 pediatric patients who underwent tOC, cOC, or ucOC measurements. Among healthy subjects, there was a positive correlation of ucOC with WC and weight, a positive correlation of tOC with FPG, HDL-c, WC, height, and weight, and a negative correlation between tOC and HbA1c. Among diabetic subjects, a negative correlation of ucOC with HbA1c and glycemia in both T1D and T2D was found and a negative correlation between tOC and HbA1c in T1D but not in T2D. The ucOC concentrations were lower in T2D, T1D, and patients with abnormal glucose status than among controls. The serum concentrations of tOC concentrations were lower among T1D than in controls. The patient's age, altitude, and HbA1c influenced the levels of serum tOC. Conclusion: Osteocalcin is involved in energy metabolism in pediatric subjects because it is consistently related to metabolic and anthropometric parameters. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42019138283.

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.

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.

[Renal transplantation program at the Centenario Hospital Miguel Hidalgo in Aguascalientes, Mexico]. / Programa de trasplante renal del centenario Hospital Miguel Hidalgo en Aguascalientes, México.

INTRODUCTION: Miguel Hidalgo Hospital in Aguascalientes is dependent from the Federal Secretary of Health and operates in integrity with State health system in Aguascalientes. It capacity is based on 132 censored beds and 71 no censored beds. Is considered a specialty hospital in the region of Bajío. Renal transplant program activity was initiated in 1990 and gives care for adult and pediatric population. MATERIAL AND METHODS: Retrospective, comparative and longitudinal study to describe and analyze our experience. Data base and clinical charts of renal transplant recipients were reviewed. Age, gender, date of transplant, etiology of renal disease, type of donor, HLA compatibility and PRA, immunosuppressive therapy, acute rejection, serum creatinina, graft loss and mortality were registered. Statistical analysis included 2, unpaired Student T test and Kaplan-Meier survival analysis with Log Rank test. Cox Analysis was also done. RESULTS: 1050 renal transplants were done from November 1990 to June 2011. 50 were excluded because follow-up was not longer than 3 months. 1000 consecutive renal transplant patients from January 1995 to June 2011 were included for analysis. Patients were divided in 2 groups: group A transplanted January 1995 to December 2004; group B transplanted January 2005 to June 2011. Etiology for end stage renal disease is unknown in 61% of cases, 11% developed renal disease to diabetes mellitus. 93% patient survival was observed at median follow-up and 84.9% graft survival at median follow-up (6 years). Biopsy proven acute rejection in group A 19.9 vs. 10% in group B. Two haplotype matching shows 92% graft survival. Diabetic patients exhibit 73% graft survival vs. other as hypertension (87%). PRA >0 and serum creatinine > 2.0 mg/dL increase risk for graft loss according to Cox analysis. CONCLUSION. Results are comparable to international data. Importance of developing regional transplant centers is emphasized.

[Prevalence of posttransplant hypertension in pediatric kidney transplant recipients: effect on long term allograft survival]. / Prevalencia de la hipertensión arterial postrasplante renal en receptores pediátricos: Efecto en la supervivencia del injerto a largo plazo.

BACKGROUND: Arterial hypertension after renal transplantation has been identified as an adverse factor over the long term allograft function, thus identification and treatment of this entity has an impact on graft survival, as in patient survival. Studies about pediatric receptor populations have reported a prevalence of hypertension after renal transplantation ranging from 58 to 90%. In Mexico, the pre-valence of arterial hypertension after renal transplantation has been reported as 71% for an adult population attending a main hospital center in Mexico. No pediatric receptor studies in Mexico have reported the prevalence of hypertension after renal transplantation so far. The purpose of our study was to document the prevalence of arterial hypertension after renal transplantation in pediatric receptors, as well as its impact on allograft survival on a long term basis. MATERIAL AND METHODS: We performed a retrospective analysis among pediatric patients who underwent renal transplantation at our center, Centenario Hospital Miguel Hidalgo, between years 2000 to 2006. RESULTS: A total of 111 pediatric renal transplantation receptors were included, among whom 56 patients were classified as hypertensive (HT) and 54 patients were classified as nomotensive (NT) (one patient had to be excluded due to early allograft dysfunction). The mean age at the time of transplantation for the population under study was 14 +/- 3 years, with a predominance of male gender over females (1.5:1). In 89% of the transplantations, the source of the allograft was a living donor. The prevalence of arterial hypertension after renal transplantation in our population was 50.5%. Among patients in the HT group at least an episode of acute rejection presented in 8.9% (n=5) of the cases, compared to only 3.7% (n=2) of patients in the NT group with an episode of acute rejection. Likewise, the prevalence of chronic allograft nephropathy detected in the HT group was 11% (n=6) vs. 7% (n=4) in the NT group. The mean serum creatinine levels were 1.0 +/- 0.4 mg/dL for the HT group and 0.9 +/- 0.3 mg/dL for the NT group at the first month followup, however mean serum creatinine levels addressed at the last consult were different among groups: 1.7 +/- 1.8 mg/dL for the HT group versus 1.1 +/- 0.5 mg/dL for the NT group. Patient survival was similar for both groups (98%) and the follow-up period was also similar, being 39 +/- 12 months for the HT group and 39 +/- 17 months for the NT group. The multivariate Cox proportional hazard analysis demonstrated that the number of antihypertensive drugs needed to achieve the control of blood pressure, and the presence of chronic allograft nephropathy, were the independent risk factors associated to a graft loss at long term. CONCLUSION: The prevalence of hypertension after renal transplantation in our pediatric population was 50.5%, which is clearly towards the inferior limit of the reported prevalence in other studies (50-90%). The tight control of blood pressure is an intervention that may have a significant impact on graft survival at long term. In our study, the severity of arterial hypertension after renal transplantation represented as the number of antihypertensive drugs needed to achieve control of blood pressure, as well as the presence of chronic allograft nephropathy, were the factors associated to long term graft loss.