Long-term follow-up of an IgA nephropathy cohort: outcomes and risk factors.

AIM: IgA nephropathy (IgAN), the most common glomerulopathy worldwide and in Uruguay, raised treatment controversies. The study aimed to analyze long-term IgAN outcomes and treatment. METHODS: A retrospective analysis of a Uruguayan IgAN cohort, enrolled between 1985 and 2009 and followed up until 2020, was performed. The Ethics Committee approved the study. The inclusion criteria were (a) biopsy-proven IgAN; (b) age ≥12 years; and (c) available clinical, histologic, and treatment data. The patients were divided into two groups, with immunosuppressive (IS) or without (NoIS) treatment. Outcomes (end-stage kidney disease/kidney replacement therapy [ESKD/KRT] or all-cause death) were obtained from mandatory national registries. RESULTS: The study population included 241 patients (64.7% men), median age 32 (19.5) years, baseline blood pressure <130/80 mmHg in 37%, and microhematuria in 67.5% of patients. Baseline proteinuria, glomerulosclerosis, and a higher crescent percentage were significantly more frequent in the IS group. Proteinuria improved in both groups. Renal survival at 20 years was 74.6% without difference between groups. In the overall population and in the NoIS group, bivariate Cox regression analysis showed that baseline proteinuria, endocapillary hypercellularity, tubule interstitial damage, and crescents were associated with a higher risk of ESKD/KRT or death, but in the IS group, proteinuria and endocapillary hypercellularity were not. In the multivariate Cox analysis, proteinuria in the NoIS group, crescents in the IS group and tubule interstitial damage in both groups were independent risk factors. CONCLUSION: The IS group had more severe risk factors than the NoIS group but attained a similar outcome.

Estimated Glomerular Filtration Rate, Albuminuria, and Adverse Outcomes: An Individual-Participant Data Meta-Analysis.

Importance: Chronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US. Objective: To evaluate associations of lower eGFR based on creatinine alone, lower eGFR based on creatinine combined with cystatin C, and more severe albuminuria with adverse kidney outcomes, cardiovascular outcomes, and other health outcomes. Design, Setting, and Participants: Individual-participant data meta-analysis of 27 503 140 individuals from 114 global cohorts (eGFR based on creatinine alone) and 720 736 individuals from 20 cohorts (eGFR based on creatinine and cystatin C) and 9 067 753 individuals from 114 cohorts (albuminuria) from 1980 to 2021. Exposures: The Chronic Kidney Disease Epidemiology Collaboration 2021 equations for eGFR based on creatinine alone and eGFR based on creatinine and cystatin C; and albuminuria estimated as urine albumin to creatinine ratio (UACR). Main Outcomes and Measures: The risk of kidney failure requiring replacement therapy, all-cause mortality, cardiovascular mortality, acute kidney injury, any hospitalization, coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The analyses were performed within each cohort and summarized with random-effects meta-analyses. Results: Within the population using eGFR based on creatinine alone (mean age, 54 years [SD, 17 years]; 51% were women; mean follow-up time, 4.8 years [SD, 3.3 years]), the mean eGFR was 90 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 11 mg/g (IQR, 8-16 mg/g). Within the population using eGFR based on creatinine and cystatin C (mean age, 59 years [SD, 12 years]; 53% were women; mean follow-up time, 10.8 years [SD, 4.1 years]), the mean eGFR was 88 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 9 mg/g (IQR, 6-18 mg/g). Lower eGFR (whether based on creatinine alone or based on creatinine and cystatin C) and higher UACR were each significantly associated with higher risk for each of the 10 adverse outcomes, including those in the mildest categories of chronic kidney disease. For example, among people with a UACR less than 10 mg/g, an eGFR of 45 to 59 mL/min/1.73 m2 based on creatinine alone was associated with significantly higher hospitalization rates compared with an eGFR of 90 to 104 mL/min/1.73 m2 (adjusted hazard ratio, 1.3 [95% CI, 1.2-1.3]; 161 vs 79 events per 1000 person-years; excess absolute risk, 22 events per 1000 person-years [95% CI, 19-25 events per 1000 person-years]). Conclusions and Relevance: In this retrospective analysis of 114 cohorts, lower eGFR based on creatinine alone, lower eGFR based on creatinine and cystatin C, and more severe UACR were each associated with increased rates of 10 adverse outcomes, including adverse kidney outcomes, cardiovascular diseases, and hospitalizations.

Mineral and bone disorder and longterm survival in a chronic kidney disease grade 3b-4cohort.

Mineral and bone disorder biomarkers 'normal ranges' are controversial. The aim of the study was to evaluate the association between serum calcium (Ca), phosphate (P), intact parathyroid hormone (iPTH), and 25(OH) vitamin D levels and mortality risk, in a chronic kidney disease (CKD) grade (G) 3b-4 cohort. The Uruguayan National Renal Healthcare Program (NRHP-UY) CKD patients' cohort, included between 1 October 2004 and 1 March 2020 and followed-up until 1 March 2021, was analyzed with the Ethics Committee approval. A total of 6473 patients were analyzed: 56% men, median age 73 (65-79) years, 55% on CKD G3b. At the end of the follow-up, 2459 (37.7%) patients had died (6.4/100 patient-year). There were iPTH data on 2013 patients (younger, with lower estimated glomerular filtration rate (eGFR) and lesser comorbidities). By bivariate Cox analysis the lowest death risk was observed with mean Ca between 9.01 and 10.25 mg/dl, P between 2.76 and 4.0 mg/dl, iPTH ≤ 105 pg/ml, and 25(OH) vitamin D >10 ng/ml. The multivariate Cox regression mortality risk adjusted to age, sex, CKD etiology, diabetes, smoking, cardiovascular comorbidity, blood pressure, proteinuria, eGFR, renin-angiotensin system blockers and vitamin D treatments, serum Ca, P, iPTH, and 25(OH) vitamin D (n = 964) showed that a higher mortality risk was associated with p > 4.00 mg/dl (HR 1.668, CI 95%: 1.201-2.317), iPTH >105 pg/ml (HR 1.386, CI 95%: 1.012-1.989), and 25(OH) vitamin D ≤ 10 ng/ml (HR 1.958, CI 95%: 1.238-3.098) and a lower mortality risk with 1,25(OH)2 vitamin D treatment (HR 0.639, CI 95%: 0.451-0.906). These data may contribute to the precise G3b-4 CKD-MBD biomarkers levels definition.

Burden of end-stage renal disease (ESRD) in Latin America.

INTRODUCTION: End-stage renal disease (ESRD) represents a major challenge for Latin America (LA). Epidemiological information needed to assist in the development of ESRD care in the region. The Latin American Dialysis and Renal Transplant Registry (RLADTR), has published several reports and its continuity has implied a sustained effort of the entire LA Nephrology community. This paper summarizes the results corresponding to year 2012. METHODS: Our methods have been reported previously. Participant countries complete an annual survey collecting data on incident and prevalent patients undergoing renal replacement treatment (RRT) in all modalities. RESULTS: 20 countries participated in the surveys, more than 90% of the Latin America. The prevalence of ESRD under RRT in LA increased from 119 patients Per million population (pmp) in 1991 to 661 pmp in 2012. HD continues to be the treatment of choice in the region (82%). A wide rate variation in incidence is observed: from 472.7 in Jalisco (Mexico) to 14 pmp in Guatemala. Diabetes remained the leading cause of ESRD. The most frequent cause of death was cardiovascular. There is a wide rate variation of nephrologist by country, from 1.8 pmp in Honduras to 45.2 pmp in Cuba. DISCUSSION: The heterogeneity or even absence of registries in some LA countries is congruent with the inequities in access to RRT in such countries, as well as the availability of qualified personnel. The SLANH is currently running training programs as well as cooperation programs between LA countries to help the least developed start ESRD programs. In this spirit, RLADTR is training personnel to carry out dialysis and transplant registries in LA.

Confirmed clinical case of chronic kidney disease of nontraditional causes in agricultural communities in Central America: a case definition for surveillance.

Over the last 20 years, many reports have described an excess of cases of chronic kidney disease (CKD) in the Pacific coastal area of Central America, mainly affecting male farmworkers and signaling a serious public health problem. Most of these cases are not associated with traditional risk factors for CKD, such as aging, diabetes mellitus, and hypertension. This CKD of nontraditional causes (CKDnT) might be linked to environmental and/or occupational exposure or working conditions, limited access to health services, and poverty. In response to a resolution approved by the Directing Council of the Pan American Health Organization (PAHO) in 2013, PAHO, the U.S. Centers for Disease Control and Prevention, and the Latin American Society of Nephrology and Hypertension (SLANH) organized a consultation process in order to expand knowledge on the epidemic of CKDnT and to develop appropriate surveillance instruments. The Clinical Working Group from SLANH was put in charge of finding a consensus definition of a confirmed clinical case of CKDnT. The resulting definition establishes mandatory criteria and exclusion criteria necessary for classifying a case of CKDnT. The definition includes a combination of universally accepted definitions of CKD and the main clinical manifestations of CKDnT. Based on the best available evidence, the Clinical Working Group also formulated general recommendations about clinical management that apply to any patient with CKDnT. Adhering to the definition of a confirmed clinical case of CKDnT and implementing it appropriately is expected to be a powerful instrument for understanding the prevalence of the epidemic, evaluating the results of interventions, and promoting appropriate advocacy and planning efforts.

Burden of disease: prevalence and incidence of ESRD in Latin America.

INTRODUCTION: Chronic kidney disease (CKD) represents a major challenge for Latin America (LA), due to its epidemic proportions and high burden to the population affected and to public health systems. METHODS: Our methods have been reported previously: This paper shows the data for the last 10 years until 2010, from the Latin American Dialysis and Renal Transplantation Registry (RLADTR). RESULTS: 20 countries participated in the surveys, covering 99% of Latin America (LA). The prevalence of end-stage renal disease (ESRD) under renal replacement therapy (RRT) in LA increased from 119 patients per million population (pmp) in 1991 to 660 pmp in 2010 (hemodialysis (HD) 413 pmp, peritoneal dialysis (PD) 135 pmp, and LFG 111 pmp). HD proportionally increased more than PD and transplant and continues to be the treatment of choice in the region (75%). The kidney transplant rate increased from 3.7 pmp in 1987 to 6.9 pmp in 1991 and to 19.1 in 2010. The total number of transplants in 2010 was 10,397, with 58% being deceased donors. The total RRT prevalence correlated positively with gross national income (GNI) (r = 0.86; p < 0.05) and life expectancy at birth (r = 0.58; p < 0.05). The global incidence rate correlated significantly only with GNI (r = 0.56; p < 0.05). Diabetes remained the leading cause of ESRD. CONCLUSION: The prevalence and incidence of RRT continues to increase. In countries with 100% public health or insurance coverage for RRT the rates are comparable to those displayed by developed countries with better GNI. PD is still an underutilized strategy for RRT in the region. Diagnostic and prevention programs for hypertension and diabetes, appropriate policies promoting the expansion of PD and organ procurement as well as transplantation as cost effective forms of RRT are needed in the region.

National kidney dialysis and transplant registries in Latin America: how to implement and improve them.

The Strategic Plan of the Pan American Health Organization, 2014-2019, Championing Health: Sustainable Development and Equityrecognizes that "Chronic kidney disease, caused mainly by complications of diabetes and hypertension, has increased in the Region." This Plan includes the first concrete goal on chronic kidney disease: to achieve a prevalence rate for renal replacement therapy of at least 700 patients per million population by 2019. National dialysis and transplant registries (DTR) are a useful tool for epidemiological research, health care planning, and quality improvement. Their success depends on the quality of their data and quality control procedures. This article describes the current situation of national DTRs in the Region and the content of their information and health indicators, and it offers recommendations for creating and maintaining them. It points to their heterogeneity or absence in some countries, in line with the inequities that patients face in access to renal replacement therapy. The complete lack of information in Caribbean countries prevents their inclusion in this communication, which requires immediate attention.

Acute kidney injury in Latin America: a view on renal replacement therapy resources.

BACKGROUND: Acute kidney injury (AKI) has increasingly been recognized as an important public health issue due to its rising frequency, its associations with early and late adverse outcomes and its economic burden. METHODS: Given the importance of determining the available resources to address this serious issue, the AKI Committee of SLANH conducted a survey to obtain information about infrastructure, human resources and equipment devoted to the treatment of AKI in Latin America RESULTS: A total of 246 units from 14 countries participated in the survey, the majority of them pertaining to nephrology divisions in teaching hospitals. Intermittent hemodialysis was universally performed by all of the units, and less frequently, slow extended dialysis (40%) and continuous renal replacement therapy (23%) were performed. Seventy-nine units (30%) perform peritoneal dialysis, but only 51 (19%) of them reported having treated at least 1 patient with this technique in the last 3 months pre-survey. The vast majority of the units reported adequate water treatment and use of modern filter membranes. Most of the patients received renal replacement therapy (RRT) in the intensive care unit. Specific causes of AKI were reported in different frequencies, with a heterogeneous pattern among the countries. Septic abortion, hemolytic-uremic syndrome, community-acquired diarrhea and leptospirosis were the etiologies most frequently associated with AKI. CONCLUSIONS: To our knowledge, this report was the first available study of the equipment and human resources utilized for RRT in AKI patients in Latin America.

The Latin American Dialysis and Renal Transplantation Registry: report 2019.

BACKGROUND: Chronic kidney disease (CKD) in Latin America (LA) continues to represent a challenge due to the burden of disease it causes and the difficulty in accessing treatment. LA has a total population of 652 million people living in 20 countries that occupy an area of 19.2 million km2. The Latin American Dialysis and Renal Transplantation Registry (LADRTR), founded in 1991, has collected data and reports on patients receiving kidney replacement therapy (KRT) since 1993. This article summarizes the registry data for 2019. METHODS: Participating countries complete an annual survey collecting aggregated data on incident and prevalent patients on KRT in all modalities. The different treatment modalities considered were hemodialysis (HD), peritoneal dialysis (PD) and living functioning kidney graft (LFG). National gross domestic product per capita (GDP, expressed in US dollars) and life expectancy at birth (LEB) corresponding to the year 2019 were collected from the World Bank Data Bank. Prevalence and incidence were compared with previous years and were also correlated with GDP and LEB. RESULTS: On 31 December 2019 a total of 432 610 patients were in KRT in LA, corresponding to an overall unadjusted prevalence of 866 per million population (pmp). Regarding treatment modality, 66.7% of the prevalent patients were treated with HD and 9.3% with PD while 24% of the patients had an LFG. A total of 85 224 patients started KRT in LA, representing a total unadjusted incidence rate of 168 pmp. Diabetic nephropathy as a cause of CKD continues to be a relevant percentage (36%) and five countries reported CKD of nontraditional causes. The kidney transplant rate in the region was 22 pmp, varying from 1 to >60 pmp. The total prevalence of KRT correlated positively with GDP per capita (r 2 = 0.6, P < 0.01) and LEB (r 2 = 0.23, P < 0.05). The overall incidence rate also significantly correlated with GDP (r 2 = 0.307, P < 0.05). The overall unadjusted mortality rate was 13%. CONCLUSION: Accessibility to KRT is still limited in LA. It is necessary to continue the efforts made by each country and the Latin American Society of Nephrology and Hypertension to guarantee equal access to treatment.

Adherence to multidisciplinary care in a prospective chronic kidney disease cohort is associated with better outcomes.

INTRODUCTION: The Renal Healthcare Program Uruguay (NRHP-UY) is a national, multidisciplinary program that provides care to chronic kidney disease (CKD) patients. In this study, we report the global results of CKD patient outcomes and a comparison between those treated at the NRHP-UY Units, with those patients who were initially included in the program but did not adhere to follow up. METHODS: A cohort of not-on dialysis CKD patients included prospectively in the NRHP-UY between October 1st 2004 and September 30th 2017 was followed-up until September 30th 2019. Two groups were compared: a) Nephrocare Group: Patients who had at least one clinic visit during the first year on NRHP-UY (n = 11174) and b) Non-adherent Group: Patients who were informed and accepted to be included but had no subsequent data registered after admission (n = 3485). The study was approved by the Ethics Committee and all patients signed an informed consent. Outcomes were studied with Logistic and Cox´s regression analysis, Fine and Gray competitive risk and propensity-score matching tests. RESULTS: 14659 patients were analyzed, median age 70 (60-77) years, 56.9% male. The Nephrocare Group showed improved achievement of therapeutic goals, ESKD was more frequent (HR 2.081, CI 95%1.722-2.514) as planned kidney replacement therapy (KRT) start (OR 2.494, CI95% 1.591-3.910), but mortality and the combined event (death and ESKD) were less frequent (HR 0.671, CI95% 0.628-0.717 and 0.777, CI95% 0.731-0.827) (p = 0.000) compared to the Non-adherent group. Results were similar in the propensity-matched group: ESKD (HR 2.041, CI95% 1.643-2.534); planned kidney replacement therapy (KRT) start (OR 2.191, CI95% 1.322-3.631) death (HR 0.692, CI95% 0.637-0.753); combined event (HR 0.801, CI95% 0.742-0.865) (p = 0.000). CONCLUSION: Multidisciplinary care within the NRHP-UY is associated with timely initiation of KRT and lower mortality in single outcomes, combined analysis, and propensity-matched analysis.

Latin American registry of renal involvement in COVID-19 disease. The relevance of assessing proteinuria throughout the clinical course.

The Latin American Society of Nephrology and Hypertension conducted a prospective cohort, multinational registry of Latin American patients with kidney impairment associated to COVID-19 infection with the objective to describe the characteristics of acute kidney disease under these circumstances. The study was carried out through open invitation in order to describe the characteristics of the disease in the region. Eight-hundred and seventy patients from 12 countries were included. Median age was 63 years (54-74), most of patients were male (68.4%) and with diverse comorbidities (87.2%). Acute kidney injury (AKI) was hospital-acquired in 64.7% and non-oliguric in 59.9%. Multiorgan dysfunction syndrome (MODS) due to COVID-19 and volume depletion were the main factors contributing to AKI (59.2% and 35.7% respectively). Kidney replacement therapy was started in 46.2%. Non-recovery of renal function was observed in 65.3%. 71.5% of patients were admitted to ICU and 72.2% underwent mechanical ventilation. Proteinuria at admission was present in 62.4% of patients and proteinuria during hospital-stay occurred in 37.5%. Those patients with proteinuria at admission had higher burden of comorbidities, higher baseline sCr, and MODS was severe. On the other hand, patients with de novo proteinuria had lower incidence of comorbidities and near normal sCr at admission, but showed adverse course of disease. COVID-19 MODS was the main cause of AKI in both groups. All-cause mortality of the general population was 57.4%, and it was associated to age, sepsis as cause of AKI, severity of condition at admission, oliguria, mechanical ventilation, non-recovery of renal function, in-hospital complications and hospital stay. In conclusion, our study contributes to a better knowledge of this condition and highlights the relevance of the detection of proteinuria throughout the clinical course.

Substitution of Oral for Intravenous Cyclophosphamide in Membranous Nephropathy.

Background: Optimal immunosuppressive treatment for membranous nephropathy is still a matter of controversy. Current recommendations include oral cyclophosphamide combined with steroids (modified Ponticelli regimen) as first-line treatment in patients who are high risk. However, concerns about the cumulative toxicity of oral cyclophosphamide persist. In the last 30 years, a protocol based on low-dose intravenous cyclophosphamide plus steroids has been used to treat membranous nephropathy in Uruguay. We aimed to assess the efficacy of this regimen to induce clinical remission in patients with membranous nephropathy. Methods: In this retrospective, observational cohort study, we analyzed the outcome of 55 patients with membranous nephropathy treated between 1990 and 2017 with a 6-month course of alternating steroids (months 1, 3, and 5) plus intravenous cyclophosphamide (single dose of 15 mg/kg on the first day of months 2, 4, and 6). Results: At 24 months, 39 (71%) patients achieved clinical response with complete remission observed in 23 patients (42%) and partial remission in 16 (29%). Median time to achieve partial and complete remission was 5.9 and 11.5 months, respectively. Absence of response was observed in 16 patients (29%), five of whom started chronic RRT after a median follow-up of 3.5 years. Clinical relapse occurred in nine of 33 (27%) patients at a median of 34 months after treatment discontinuation. Conclusions: Replacement of oral cyclophosphamide with a single intravenous pulse on months 2, 4, and 6 of the modified Ponticelli regimen can be an effective and safe alternative for treatment of membranous nephropathy. Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/K360/2020_09_24_KID0002802020.mp3.

EPILAT-IRA Study: A contribution to the understanding of the epidemiology of acute kidney injury in Latin America.

INTRODUCTION: Epidemiology of acute kidney injury (AKI) is highly dependent on patient characteristics, context and geography. Considering the limited information in Latin America and the Caribbean, we performed a study with the aim to contribute to improve its better understanding. METHODS: Observational, prospective, longitudinal, multinational cohort study addressed to determine risk factors, clinical profile, process of care and outcomes of AKI in the region. Patients meeting KDIGO AKI definition were included over a 9-month period and designated community or hospital-acquired. De-identified clinical and lab data were entered in a specifically designed on-line platform. Co-variables potentially linked to AKI onset, in-hospital and 90-days mortality, were recorded and correlated using a multiple logistic regression model. RESULTS: Fifty-seven physicians from 15 countries provided data on 905 patients, most with acceptable basic needs coverage. Median age 64 (50-74) yrs; most of them were male (61%) and mestizos (42%). Comorbidities were present in 77%. AKI was community-acquired in 62%. Dehydration, shock and nephrotoxic drugs were the commonest causes. During their process of care, 77% of patients were assessed by nephrologists. Kidney replacement therapy (KRT) was performed in 29% of cases. In-hospital mortality was 26.5% and independently associated to older age, chronic liver disease, hypotension, shock, cardiac disturbances, hospital-acquired sepsis, KRT and mechanical ventilation. At 90-days follow up partial or complete renal recovery was 81% and mortality 24%. CONCLUSIONS: AKI was mainly community-acquired, in patients with comorbidities and linked to fluid loss and nephrotoxic drugs. Mortality was high and long-term follow up poor. Notwithstanding, the study shows partially the situation in the participant countries rather than the actual epidemiology of AKI in Latin America and Caribbean, a pending and needed task.

Risk factors profile for acute kidney injury after cardiac surgery is different according to the level of baseline renal function.

Acute kidney injury (AKI) occurs frequently after cardiac surgery. Although numerous variables were identified as predictors for AKI, there is a lack of information about possible differences in risk factors according to the level of preoperative renal function. Preoperative, intraoperative, and postoperative data from 4118 adult patients submitted to cardiac surgery from January 1, 2000, to December 31, 2005, were included in the study. AKI was defined by an increase in serum creatinine (S(Cr)) >/= 0.3 mg/dL after surgery. Patients were stratified into two groups: group 1, C(Cr) >/= 60 mL/min/1.73 m(2) BSA; group 2, C(Cr) < 60 mL/min/1.73 m(2) BSA. Risk factors were assessed using a multiple logistic regression model. In all, 749 patients (42.5%) developed AKI. The mortality rate of the entire population was a 5.2%. In patients of group 1 (n = 2678), the variables independently associated with the onset of AKI were age, diabetes, preoperative use of diuretics, non-scheduled surgery, cardiopulmonary by-pass (CPB) time, CPB mean arterial pressure, hemodilution, and postoperative use of norepinephrine. Baseline S(Cr) was associated with AKI only in patients of group 2 (n = 1440). Age, EuroSCORE, non-coronary surgery, hemodilution, and postoperative use of vasoactive drugs were also predictors of AKI in this group of patients. The mortality rate was significantly higher in group 2 than group 1 (8.5% vs. 3.6%, p = 0.000). In conclusion, the present study demonstrated a difference in variables associated with postoperative AKI, according to baseline renal function. The degree of preoperative renal function was a predictor of AKI only in patients with CKD stages 3-4, as well as other risk factors. In addition to other well known risk factors for AKI in this setting, the use of diuretics in patients of group 1 and the level of hemodilution during CPB in both groups should be emphasized, as they are potentially modifiable.

Phylogeography of screaming hairy armadillo Chaetophractus vellerosus: Successive disjunctions and extinctions due to cyclical climatic changes in southern South America.

Little is known about phylogeography of armadillo species native to southern South America. In this study we describe the phylogeography of the screaming hairy armadillo Chaetophractus vellerosus, discuss previous hypothesis about the origin of its disjunct distribution and propose an alternative one, based on novel information on genetic variability. Variation of partial sequences of mitochondrial DNA Control Region (CR) from 73 individuals from 23 localities were analyzed to carry out a phylogeographic analysis using neutrality tests, mismatch distribution, median-joining (MJ) network and paleontological records. We found 17 polymorphic sites resulting in 15 haplotypes. Two new geographic records that expand known distribution of the species are presented; one of them links the distributions of recently synonimized species C. nationi and C. vellerosus. Screaming hairy armadillo phylogeographic pattern can be addressed as category V of Avise: common widespread linages plus closely related lineages confined to one or a few nearby locales each. The older linages are distributed in the north-central area of the species distribution range in Argentina (i.e. ancestral area of distribution). C. vellerosus seems to be a low vagility species that expanded, and probably is expanding, its distribution range while presents signs of genetic structuring in central areas. To explain the disjunct distribution, a hypothesis of extinction of the species in intermediate areas due to quaternary climatic shift to more humid conditions was proposed. We offer an alternative explanation: long distance colonization, based on null genetic variability, paleontological record and evidence of alternance of cold/arid and temperate/humid climatic periods during the last million years in southern South America.

Raising Awareness of Acute Kidney Injury: A Latin American Experience.

INTRODUCTION: Raising awareness of acute kidney injury (AKI) is an essential strategy for minimizing the burden of this lethal syndrome. The AKI Commission of the Latin American Society of Nephrology and Hypertension conducted an educational program based on networked learning. METHODS: Two online courses with similar methodologies were developed, 1 course for nephrologists and the other for primary care physicians (PCP). The courses were developed as a distance education, asynchronous online modality with multiple educational strategies: written lessons, videos, e-rounds, and clinical simulation. Knowledge gain was explored through a 10-question test before and after course completion. RESULTS: The course for nephrologists had 779 participants from 21 countries; 52% were male, and 46% were <35 years of age. Mean qualification increased from 5.87 to 8.01 (36% gain of knowledge). The course for PCPs had 2011 participants, 81% of whom were physicians. The time from graduation was <5 years in 52%. In both courses, clinical simulation was considered the best part and lack of time the main limitation for learning. Because 48% of the nephrologist course attendees were interested in AKI activities, a Latin American AKI Network site (RedIRA) composed of a brief review, a clinical forum, a self-assessment, and a bibliography on AKI was launched on a monthly basis in November 2016. To date there are 335 users from 18 countries. CONCLUSIONS: Distance education techniques were effective for learning about AKI and are a potential tool for the development of a sustainable structure for communication, exchange, and integration of physicians involved in the care of patients with AKI.

Acute kidney injury after cardiac surgery is associated with mid-term but not long-term mortality: A cohort-based study.

Acute kidney injury (AKI) in cardiac surgery is associated with complications, early and late mortality and increased health care expenditures. The overall dynamic comorbidity-adjusted contributions of an episode of AKI on mortality during long-term follow-up have not been fully explored. A longitudinal cohort of 7075 adult patients admitted for cardiac surgery were enrolled in the study. Follow-up data were obtained through telephonic survey after 1, 5, 10, and 15 years or from the National Mortality Registry. All-cause mortality was assessed at five time intervals: I) 30 days after surgery to 1 year; II) 1 to 3 years; III) 3 to 5 years; IV) 5 to 10 years; and V) 10 to 15 years. For the adjustment of mortality for comorbidity and pre-, intra- and postoperative variables, Cox proportional hazard regression models were conducted within each period. The overall incidence of AKI was 36.1%. AKI was an independent predictor of death only during the first five years after surgery (30 days to 1 year: HR 1.834, 95% CI 1.459 to 2.306; 1 to 3 years: HR 1.285, 95% CI 1.023 to 1.610; and 3 to five years: HR 1.330, 95% CI 1.123 to 1.750). Only age, diabetes mellitus and CHF were associated with increased risk of death over the entire follow-up period. Our study demonstrates a transient association of AKI with long-term mortality that progressively decreases and vanishes five years after surgery. The knowledge of this dynamic is crucial to understanding this complex association, planning health care and allocating resources.

Acute Kidney Injury in Mechanically Ventilated Patients: The Risk Factor Profile Depends on the Timing of Aki Onset.

BACKGROUND: Acute kidney injury (AKI) is a frequent complication in patients under mechanical ventilation (MV). We aimed to assess the risk factors for AKI with particular emphasis on those potentially preventable. STUDY DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of a large, multinational database of MV patients with >24 h of MV and normal renal function at admission. AKI was defined according to creatinine-based KDIGO criteria. Risk factors were analyzed according to the time point at which AKI occurred: early (≤48 h after ICU admission, AKIE) and late (day 3 to day 7 of ICU stay, AKIL). A conditional logistic regression model was used to identify variables independently associated with AKI. RESULTS: Three thousand two hundred six patients were included. Seven hundred patients had AKI (22%), the majority of them AKIE (547/704). The risk factor profile was highly dependent upon the timing of AKI onset. In AKIE risk factors were older age; SAPS II score; postoperative and cardiac arrest as the reasons for MV; worse cardiovascular SOFA, pH, serum creatinine, and platelet count; higher level of peak pressure and Vt/kg; and fluid overload at admission. In contrast, AKIL was linked mostly to events that occurred after admission (lower platelet count and pH; ICU-acquired sepsis; and fluid overload). None ventilation-associated parameters were identify as risk factors for AKIL. CONCLUSIONS: In the first 48 h, risk factors are associated with the primary disease and the patient's condition at admission. Subsequently, emergent events like sepsis and organ dysfunction appear to be predictive factors making prevention a challenge.

Effectiveness and safety of a 6-month treatment with paricalcitol in patients on hemodialysis with secondary hyperparathyroidism.

Introduction: The mineral bone disorder, particularly secondary hyperparathyroidism, in chronic kidney disease (CKD) has a systemic impact affecting not only bone metabolism. Therefore its correction is important to prevent cardiovascular, inflammatory and immune diseases. Objective: To assess the effectiveness and safety of intravenous paricalcitol administered over a 6 month period for the treatment of secondary hyperparathyroidism (SHPT) in patients undergoing conventional hemodialysis, with close follow-up of treatment response. Methods: A phase 4 clinical trial was performed comparing clinical and laboratory data before and after 6 months of treatment. SHPT patients undergoing hemodialysis who were naïve to vitamin D metabolites or had failed to current therapy were included. Clinical and laboratory characteristics were analyzed. Efficacy analyses were based on intact parathyroid hormone (iPTH) levels and were performed using data from patients who completed 6 months of treatment. Results: Nineteen of the 26 patients enrolled completed 6 months of treatment. All patients exhibited reduced baseline iPTH levels (mean reduction, 371.8 pg/mL; 95% CI, 273.3-470.2 pg/mL]; 17 patients (89.5%) had reductions exceeding 30%. Twelve patients (63%) achieved therapeutic success (defined as iPTH serum levels 150-300 pg/mL), with a median time of 2 months from the beginning of treatment. All reported episodes of hypercalcemia (n = 2) and hyperphosphatemia (n = 34) were asymptomatic. No major therapy-related serious AEs were reported. Conclusion: Paricalcitol was safely administered and was associated with significant decreases in iPTH levels over the study period.

Introdução: A doença metabólica óssea, em particular o hiperparatireoidismo secundário, na doença renal crônica (DRC) tem um impacto sistêmico que afeta nem só o metabolismo ósseo. Por tanto, sua correção é importante para prevenir as doenças do sistema imunitário, inflamatório e cardiovascular. Objetivo: Avaliar a eficácia e a segurança do paricalcitol intravenoso administrado durante um período de 6 meses no tratamento do hiperparatireoidismo secundário (SHPT) em pacientes submetidos a hemodiálise convencional, com acompanhamento de perto da resposta do tratamento. Métodos: Realizou-se um ensaio clínico de fase 4 que comparava os dados clínicos com os dados do laboratório antes e depois dos 6 meses de tratamento. Incluíram-se os pacientes SHPT em hemodiálise sem experiência com os metabólitos da vitamina D ou que fracassaram com a terapia em uso. Analisaram-se as características clínicas e de laboratório. As análises de eficácia se basearam nos níveis do hormônio da paratireóide intacto (iPTH) e foram realizadas usando dados dos pacientes que completaram os 6 meses de tratamento. Resultados: Dezenove dos 26 pacientes registrados completaram os 6 meses de tratamento. Todos os pacientes mostraram níveis de referência iPTH reduzidos (redução média, 371,8 pg/mL; 95% CI, 273,3-470.2 pg/mL]; 17 pacientes (89,5%) tiveram reduções superiores a 30%. Doze pacientes (63%) conseguiram o sucesso terapêutico (definido como níveis de soros iPTH de 150-300 pg/mL), com um tempo médio de 2 meses a partir do início do tratamento. Todos os episódios de hipercalcemia (n = 2) e de hiperfosfatemia (n = 34) reportados foram assintomáticos. Não se informaram AEs graves importantes relacionados à terapia. Conclusão: O paricalcitol foi administrado de forma segura e se associou às reduções significativas nos níveis de iPTH durante o período do estudo.