Chronic Kidney Disease Stage and Cardiovascular and Mortality Events Among Older Adults: The SPRINT Trial.

Rationale & Objective: The risk implications of the Kidney Disease: Improving Global Outcomes (KDIGO) chronic kidney disease classification in older adults are controversial. We evaluated the risk of adverse outcomes in this population across categories of estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR). Study Design: Prospective cohort. Settings & Participants: In total, 2,509 participants aged ≥75 years in the Systolic Blood Pressure Intervention Trial (SPRINT). Exposure: KDIGO eGFR and UACR categories. We combined KDIGO categories G1 and G2, G3b and G4, as well as A2 and A3. Outcomes: Primary SPRINT outcome (composite of myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes), and all-cause death. Analytical Approach: Multivariable Cox proportional hazard models. Results: Mean age was 79.8 years, and 37.4% were female. The mean eGFR was 64.0 mL/min/1.73 m2, and the median UACR was 13.1 mg/g. In multivariable Cox proportional hazard analysis, compared with participants with eGFR ≥ 60 mL/min/1.73 m2 and UACR < 30 mg/g, there was no statistically significant difference in the risk of the primary outcome among participants with eGFR 45-59 or 15-44 mL/min/1.73 m2 and UACR < 30 mg/g. However, those with eGFR 45-59 or 15-44 mL/min/1.73 m2 and UACR ≥ 30 mg/g had higher risk of the primary outcome (HR [95% CI], 1.97 [1.27-3.04] and 3.32 [2.23-4.93], respectively). The risk for all-cause death was higher for each category of abnormal eGFR and UACR, with the highest risk observed among those with eGFR 15-44 mL/min/1.73 m2 and UACR ≥ 30 mg/g (3.34 [2.05-5.44]). Limitations: Individuals with diabetes and urine protein >1 g/day were excluded from SPRINT. Conclusion: Among older adults SPRINT participants, low eGFR without albuminuria was associated with higher mortality but not with increased risk of cardiovascular events. Additional studies are needed to evaluate an adapted chronic kidney disease stage-based risk stratification for older adults.

Using data from participants in the SPRINT trial, we evaluated the association of chronic kidney disease stage with adverse clinical outcomes among adults older than 75 years without diabetes. We found that low level of kidney function determined by a low estimated glomerular filtration rate with moderately or severely increased urine albumin excretion was associated with increased risk for cardiovascular events and all-cause mortality. However, low estimated glomerular filtration rate with normal or mildly increased urinary albumin excretion was not consistently associated with these adverse outcomes. This finding supports the need for additional studies to evaluate an age-adapted classification of chronic kidney disease to improve risk stratification among older adults.

Atypical Hemolytic Uremic Syndrome: A Nationwide Colombian Pediatric Series.

Objectives. Atypical hemolytic uremic syndrome (aHUS) is a rare complement-mediated kidney disease with genetic predisposition and represents up to 10% of pediatric hemolytic uremic syndrome (HUS) cases. Few studies have evaluated aHUS in Latin American population. We studied a Colombian pediatric cohort to delineate disease presentation and outcomes. Methods. A multicenter cohort of 27 Colombian children with aHUS were included. Patients were grouped by age at onset. Clinical features were compared using analysis of variance (ANOVA) and Fisher exact tests. Renal biopsy was performed on 6 patients who were suspected of having other renal diseases before aHUS diagnosis. Results. Most patients were male (70%). The onset of aHUS occurred frequently before age 4 years (60%) and followed gastroenteritis as the main triggering event (52%). Age groups showed comparable clinical presentation, disease severity, treatment, and outcomes. Pulmonary involvement (67%) was the main extrarenal manifestation, particularly in the 1 to 7 age group (P = .01). Renal biopsies were as follows: 3 had membranoproliferative glomerulonephritis (MPGN) type I, one MPGN type III, one C3-glomerulonephritis, and one rapidly progressive GN. Genetic screening was available in 6 patients and identified 2xCFHR5, 2xMCP, 1xADAMTS13/THBD, and 1xDGKE mutations. A total of 15 relapses were seen, of which 8 (72%) occurred in the 1 to 7 age group. The renal outcome was not significantly different regardless of age group. Conclusion. In our cohort, we observed a relatively high frequency of extrarenal involvement at first presentation represented by pulmonary manifestations. The renal prognosis at initial presentation was worse than in previous reports.

Obesity and glomerular filtration rate.

Obesity has received considerable attention in general medicine and nephrology over the last few years. This condition increases the risk of metabolic syndrome, diabetes mellitus, hypertension, and dyslipidemia, which are the main risk factors for developing chronic kidney disease (CKD). Kidney damage caused by obesity can be explained by many mechanisms, such as sympathetic nervous and renin-angiotensin-aldosterone systems activation, mechanical stress, hormonal unbalance, as well as inflammatory cytokines production. Even though creatinine-based glomerular filtration rate (GFR) equations in obese individuals have been validated (Salazar-Corcoran and CKD-MCQ), changes in body weight after bariatric surgery (BS) leads to changes in creatininemia, affecting its reliability. Thus, an average between creatine and cystatin-based GFR equations would be more appropriate in this setting. Bariatric surgery can reverse diabetes mellitus and improve hypertension, which are the main causes of CKD. Conclusion: GFR can be affected by obesity and BS, and its value should be cautiously evaluated in this setting.

Alactic base excess is an independent predictor of death in sepsis: A propensity score analysis.

PURPOSE: Alactic base excess (ABE) is a novel biomarker defined as the sum of lactate and standard base excess and estimates the renal capability of handling acid-base disturbances in sepsis. The objective of this study is to see if ABE is an independent predictor of mortality in septic patients with and without renal dysfunction. MATERIALS AND METHODS: We retrospectively studied 1178 patients with sepsis and septic shock. Patients were divided according to ABE values: 1) negative ABE (<-3 mmol/L); 2) neutral ABE (≥ - 3 and < 4 mmol/L); and 3) positive ABE (≥4 mmol/L). The effect of ABE on mortality was evaluated using Cox regression weight by inverse probability weighting (IPWT) analysis after propensity score assessment. Additionally, we performed a stratified analysis in patients with GFR > 60 mL/min/1.73 m2. RESULTS: Negative ABE patients had higher mortality than patients with neutral ABE (adjusted HR 1.43; 95%CI 1.02-2.01). Also, in patients with GFR > 60 mL/min/1.73 m2 (n = 493), we observed higher mortality in patients with negative ABE (adjusted HR 2.43; 95%CI 1.07-5.53). CONCLUSIONS: Negative ABE is an independent predictor of in-hospital mortality in septic patients with and without renal dysfunction.

Renal tubular dysfunction in COVID-19 patients.

INTRODUCTION: SARS-CoV-2 infection can affect other organs aside from those of respiratory system, particularly the kidney, heart, blood, digestive tract, and nervous system. COVID-19 renal compromise consists of different syndromes since proteinuria, hematuria, and acute kidney injury (AKI), until chronic kidney disease. Since COVID-19-induced renal tubular damage has been described as a potential antecedent condition to AKI installation, it was decided to evaluate how COVID-19 affects tubular function. MATERIALS AND METHOD: Serum inflammatory parameters, urinalysis, and classical urinary indexes in COVID-19 admitted patients who had neither AKI nor chronic kidney disease (CKD) were evaluated. Statistical analysis was performed by applying Student t test. RESULTS: Renal tubular function was evaluated in 41 COVID-19 admitted patients who had neither AKI nor CKD. Patients' mean age was 56 years, males (79%), and with normal creatininemia (0.8 ± 0.2 mg/dL) and eGFR (105.7 ± 6.5 mL/min) values. It was found mild hypocalcemia and a relative increased fractional excretion (FE) of sodium, FE of calcium, FE of phosphorus, calcium-creatinine index, urinary osmolarity, and relative alkaline urine pH values. CONCLUSION: Tubular dysfunction was documented in COVID-19 patients.

Nocturia: its characteristics, diagnostic algorithm and treatment.

Nocturia is the complaint that an individual has to wake up at night one or more times to urinate. It is a frequent condition among older adults and entails detrimental effects with regard to sleeping, sexual activity, comfort, depression, mental function and vitality. It is clinically important to distinguish it from global polyuria, defined as a urinary rate ≥ 125 ml/h (3000 ml/day), as well as from nocturnal polyuria, which is an abnormally large volume of urine during sleep associated with a decreased daytime urine production. A Frequency Volume Chart (FVC), overnight water deprivation test with renal concentrating capacity test, and the nocturnal bladder capacity index are some of the methods that help establish the underlying pathology of this condition and hence define an adequate treatment plan.

Chronic kidney disease (CKD) and chronic kidney insufficiency (CKI) diagnosing equation in cirrhotic patients.

Cirrhotic patients can develop acute kidney injury (AKI), and chronic kidney disease (CKD). Therefore, renal functional evaluation is crucial in cirrhotic patients. However, serum creatinine and urea levels, as well as measured or estimated glomerular filtration rate is not reliable renal functional markers in these patients compared to other patient groups. In the present study, four original equations are designed and tested for screening chronic kidney disease (CKD) and chronic kidney insufficiency (CKI) in stable cirrhotic patients. MATERIAL & METHOD: estimated GFR (CKD-EPI creatinine and cystatin equations) were recorded in 175 adult stable patients suffering from cirrhosis, and these patients were classified as presenting or not CKD and CKI after evaluation by two independent nephrologists. Based on these data, the variables with the significant discriminating capability to identify CKD and CKI (based on creatinine and cystatin) were detected by applying the Student's t-test for two independent groups, later confirmed by the lambda test of Wilks, in order to obtain the renal function equations. RESULTS: CKD equation (creatinine) = 7.094238-0.043104 × CKD-EPI creatinine - 0.057537 × haematocrit. CKD equation (cystatin) = 8.375074-0.117218 × CKD-EPI cystatin. CKI equation (creatinine) = 0.428389-0.043214 × CKD-EPI creatinine +0.183051 × Child-Pugh score + 0.050162 × age (in years). CKI equation (cystatin) = 9.169579-0.139319 × CKD-EPI cystatin. CONCLUSION: Simple and reliable equations have been obtained for screening chronic kidney disease and chronic kidney insufficiency in cirrhotic patients.

Differences between COVID-19-induced acute kidney injury and chronic kidney disease patients / Diferenças entre pacientes com lesão renal aguda induzida por COVID-19 e pacientes com doença renal crônica

Abstract Introduction: This article describes the main differences between COVID-19-induced acute kidney injury (AKI-COVID19) in patients with previous normal renal function (AKI-NRF) and those with chronic kidney disease (AKI-CKD) treated in a high complexity clinic in Barranquilla (Colombia). Material and Methods: The patients included in this study (n: 572) were those with a positive diagnosis of COVID-19 confirmed by detection of a positive PCR for SARS-CoV-2. Of these patients, 188 developed AKI during their hospital stay. Patients' epidemiological data, serum parameters, and clinical frailty status were recorded. Statistical analysis and comparison among AKI-NRF, AKI-CKD, and non-AKI patients were performed. Results: The incidence of COVID-19-induced AKI was 33%, with the majority classified as AKIN 1, 16% requiring renal replacement therapy, and AKI-COVID19 mortality of 68%. A significantly higher prevalence of hypertension, cardiac disease, and serum reactive C-protein and lower albumin values in AKI-CKD patients was recorded. Mortality rate, invasive ventilation requirement, and D-dimer levels were significantly higher in AKI-NRF patients: Conclusion: Different clinical patterns between AKI-NRF and AKI-CKD were documented.

Resumo Introdução: Este artigo descreve as principais diferenças entre a lesão renal aguda induzida por COVID-19 (LRA-COVID19) em pacientes com função renal normal prévia (LRA-FRN) e aqueles com doença renal crônica (LRA-DRC) atendidos em uma clínica de alta complexidade em Barranquilla (Colômbia). Material e Métodos: Os pacientes incluídos neste estudo (n: 572) foram aqueles com um diagnóstico positivo de COVID-19 confirmado pela detecção de PCR positivo para SARS-CoV-2. Destes pacientes, 188 desenvolveram LRA durante sua internação. Foram registrados os dados epidemiológicos, os parâmetros séricos e o estado de fragilidade clínica dos pacientes. Foram feitas a análise estatística e a comparação entre pacientes com LRA-FRN, LRA-DRC, e pacientes sem LRA. Resultados: A incidência de LRA induzida por COVID-19 foi de 33%, com a maioria classificada como AKIN 1, 16% exigindo terapia renal substitutiva, e a mortalidade por LRA-COVID19 foi de 68%. Foi registrada uma prevalência significativamente mais alta de hipertensão, doença cardíaca e proteína C reativa sérica e valores mais baixos de albumina em pacientes com LRA-DRC. A taxa de mortalidade, a necessidade de ventilação invasiva e os níveis de dímero-D foram significativamente mais altos em pacientes com LRA-FRN. Conclusão: Foram documentados padrões clínicos diferentes entre LRA-FRN e LRA-DRC.

Tasa de filtración glomerular conservada en personas mayores. Un estudio de base poblacional en el Cono Sur de América Latina

Introduction: Kidneys are affected by the aging process, usually suffering a progressive glomerular filtration rate (GFR) reduction of around 1 ml/year as of 30 years of age. Nevertheless, few older subjects show a stable GFR over time. This phenomenon has not been exhaustively studied, and even less in the Southern Cone. Aim: The aim was to estimate the prevalence of preserved GFR in a representative sample of older adults and explore the association between cardiovascular risk factors and preserved GFR in older individuals. Methods: We used data from a cross-sectional survey of a random sample of 1571 participants aged 65-74 years from 4 cities of the Southern Cone. We describe the prevalence of eGFR ≥80 ml/min/1.73 m2 and sociodemographic, biological, behavioral risk factors and medication use. Backward stepwise logistic regression analysis was used to study the effect of cardiovascular risk factors on eGFR ≥80 ml/min. Results: In this study, 962 had an eGFR >80 ml/min/1.73 m2 and 154 were healthy adults (Prevalence= 17.01% (95%CI 14.5%; 19.9%)). The median eGFR in the full sample was 85.53 ml/min/1.73 m² (IQR: 73.12-91.26). The prevalence of eGFR >80 ml/min/1.73 m2 was higher among men. Overall, older adults with no cardiovascular risk factors and eGFR >80 ml/min/1.73 m2 were predominantly men and showed a lower prevalence of dyslipidemia. Conclusion: The present study documented that 17% of healthy older individuals have preserved glomerular filtration rate (eGFR>80 ml/min/1.73 m2) despite their advanced age.

Introducción: Los riñones se ven afectados por el proceso de envejecimiento, sufriendo habitualmente una reducción progresiva de la tasa de filtración glomerular (TFG) de alrededor de 1 ml/año a partir de los 30 años de edad. Sin embargo, son pocos los sujetos de edad avanzada que muestran una TFG estable a lo largo del tiempo. Este fenómeno no ha sido estudiado exhaustivamente, y menos aún en el Cono Sur. Objetivo: El objetivo fue estimar la prevalencia de la TFG conservada en una muestra representativa de adultos mayores y explorar la asociación entre los factores de riesgo cardiovascular y la TFG conservada en individuos de edad avanzada. Métodos: Utilizamos datos de una encuesta transversal de una muestra aleatoria de 1571 participantes de 65-74 años de edad de 4 ciudades del Cono Sur. Describimos la prevalencia de FGe ≥80 ml/min/1,73 m2 y los factores de riesgo sociodemográficos, biológicos y conductuales y el uso de medicamentos. Se utilizó un análisis de regresión logística por pasos hacia atrás para estudiar el efecto de los factores de riesgo cardiovascular sobre la TFGe ≥80 ml/min. Resultados: En este estudio, 962 tenían una TFGe >80 ml/min/1,73 m2 y 154 eran adultos sanos (Prevalencia= 17,01% (IC 95% 14,5%; 19,9%)). La mediana de la TFGe en la muestra completa fue de 85,53 ml/min/1,73 m² (IQR: 73,12-91,26). La prevalencia de la TFGe >80 ml/min/1,73 m2 fue mayor entre los hombres. En general, los adultos mayores sin factores de riesgo cardiovascular y con una TFGe >80 ml/min/1,73 m2 eran predominantemente hombres y mostraban una menor prevalencia de dislipidemia. Conclusiones: El presente estudio documentó que el 17% de los individuos mayores sanos tienen una tasa de filtración glomerular preservada (TFGe>80 ml/min/1,73 m2) a pesar de su avanzada edad.

Glomerular Diseases in the Colombian Caribbean: Data from the Colombian Nephropathy Registry (NEFRORED®).

Our study aimed to describe the glomerular diseases, both primary glomerular disease (PGD) and secondary glomerular disease (SGD) in the Colombian Caribbean based on the first regional Colombian Nephropathy Registry (NEFRORED®). A descriptive and retrospective study of adult patients with glomerular diseases from the Colombian Caribbean region was made. All diagnoses by renal biopsy with light microscopy and immunofluorescence obtained between January 2008 and June 2018 were recorded. Eight hundred and seventy-one renal biopsies were obtained. The main clinical indication for biopsy was nephritic syndrome (36%). SGD was more frequent than PGD (55% vs. 45%). Within SGD group, lupus nephritis (LN) was the most frequent etiology (83%). Within PGD group, membranous nephropathy (33%) and focal segmental glomerulosclerosis (FSGS) (19%) were the most common glomerular diseases. At a 24-month follow-up, the patients with FSGS and paraproteinemia-mediated glomerular disease had the worst renal survival prognosis. This is the first Colombian Nephropathy Registry in a Caribbean population, demonstrating a high predominance of SGD due to LN.

Medicina biosemiótica: de una medicina de efectos a una medicina de procesos / Biosemiotic medicine: From an effect-based medicine to a process-based medicine

La medicina contemporánea se caracteriza por una creciente subespecialización, así como por la adquisición de un mayor conocimiento respecto de la interacción entre las distintas estructuras del organismo (biosemiótica) tanto en estado de salud como de enfermedad. Se propone, en este artículo, una nueva conceptualización del organismo basada en la perspectiva de considerarlo conformado por un espacio biológico (células, tejidos y órganos) y un espacio biosemiótico (intercambio de señales entre ellos). Su desarrollo daría lugar a una nueva subespecialidad dedicada al estudio e interferencia de la biosemiótica de la enfermedad (medicina biosemiótica), lo que propiciaría el desarrollo de una medicina de procesos, tendiente al diagnóstico y tratamiento temprano de las enfermedades

Contemporary medicine is characterized by an increasing subspecialization and the acquisition of a greater knowledge about the interaction among the different body structures (biosemiotics), both in health and disease. This article proposes a new conceptualization of the body based on considering it as a biological space (cells, tissues, and organs) and a biosemiotic space (exchange of signs among them). Its development would lead to a new subspecialty focused on the study and interference of disease biosemiotics (biosemiotic medicine), which would trigger a process-based medicine centered on early diagnosis and management of disease.

Osmotic diuresis in chronic kidney disease: its significance and clinical utility.

INTRODUCTION: The kidneys contribute to maintain plasma osmolality in normal range by achieving the adequate daily osmolar urine excretion (DOUE). An equation has been described for estimating the expected daily urine volume necessary to excrete the osmolar load required to keep serum osmolality in normal range. According to this equation, a difference between real and expected daily osmolar diuresis (DOD) can be obtained, being normally this difference value zero (± 500 cc). However, a positive DOD difference signifies a reduced urine concentration capability, while a negative DOD difference signifies a reduced urine dilution capability. Therefore, we decided to originally investigate how DOUE, and DOD difference are modified through the different stages of CKD. MATERIALS AND METHODS: 61 patients suffering from CKD (stages I-V) secondary to glomerulopathies were studied. Creatinine clearance (CrCl), DOUE, and difference between real and expected DOD were obtained from each patient. Besides, correlation (Spearman) between CrCl and DOUE, and between CrCl and real-expected DOD difference were also obtained. RESULTS: Spearman correlation between CrCl and DOUE was positive and significant (Spearman's ρ = 0.63, p < 0.0001). In addition, CKD patients who were not able to achieve the minimal DOUE required (600 mOsm/day) were mostly those with CrCl < 40 mL/min. Spearman correlation between CrCl and real-expected DOD difference was negative and significant (Spearman's ρ = - 0.4, p < 0.0013). Additionally, abnormal DOD difference (> 500 cc) was found in CKD patients with CrCl < 80 mL/min/1.73 m2. CONCLUSION: Daily osmolar urine excretion, and difference between real and expected daily osmolar diuresis are simple and significant clinical parameter which can be useful to easily evaluate urine concentration-dilution capability (tubular function) in CKD patients.