Albuminuria, Forgotten No More: Underlining the Emerging Role in CardioRenal Crosstalk.

Kidneys have an amazing ability to adapt to adverse situations, both acute and chronic. In the presence of injury, the kidney is able to activate mechanisms such as autoregulation or glomerular hyperfiltration to maintain the glomerular filtration rate (GFR). While these adaptive mechanisms can occur in physiological situations such as pregnancy or high protein intake, they can also occur as an early manifestation of diseases such as diabetes mellitus or as an adaptive response to nephron loss. Although over-activation of these mechanisms can lead to intraglomerular hypertension and albuminuria, other associated mechanisms related to the activation of inflammasome pathways, including endothelial and tubular damage, and the hemodynamic effects of increased activity of the renin-angiotensin-aldosterone system, among others, are recognized pathways for the development of albuminuria. While the role of albuminuria in the progression of chronic kidney disease (CKD) is well known, there is increasing evidence of its negative association with cardiovascular events. For example, the presence of albuminuria is associated with an increased likelihood of developing heart failure (HF), even in patients with normal GFR, and the role of albuminuria in atherosclerosis has recently been described. Albuminuria is associated with adverse outcomes such as mortality and HF hospitalization. On the other hand, it is increasingly known that the systemic effects of congestion are mainly preceded by increased central venous pressure and transmitted retrogradely to organs such as the liver or kidney. With regard to the latter, a new entity called congestive nephropathy is emerging, in which increased renal venous pressure can lead to albuminuria. Fortunately, the presence of albuminuria is modifiable and new treatments are now available to reverse this common risk factor in the cardiorenal interaction.

Pathophysiology of bone disease in chronic kidney disease: from basics to renal osteodystrophy and osteoporosis.

Chronic kidney disease (CKD) is a highly prevalent disease that has become a public health problem. Progression of CKD is associated with serious complications, including the systemic CKD-mineral and bone disorder (CKD-MBD). Laboratory, bone and vascular abnormalities define this condition, and all have been independently related to cardiovascular disease and high mortality rates. The "old" cross-talk between kidney and bone (classically known as "renal osteodystrophies") has been recently expanded to the cardiovascular system, emphasizing the importance of the bone component of CKD-MBD. Moreover, a recently recognized higher susceptibility of patients with CKD to falls and bone fractures led to important paradigm changes in the new CKD-MBD guidelines. Evaluation of bone mineral density and the diagnosis of "osteoporosis" emerges in nephrology as a new possibility "if results will impact clinical decisions". Obviously, it is still reasonable to perform a bone biopsy if knowledge of the type of renal osteodystrophy will be clinically useful (low versus high turnover-bone disease). However, it is now considered that the inability to perform a bone biopsy may not justify withholding antiresorptive therapies to patients with high risk of fracture. This view adds to the effects of parathyroid hormone in CKD patients and the classical treatment of secondary hyperparathyroidism. The availability of new antiosteoporotic treatments bring the opportunity to come back to the basics, and the knowledge of new pathophysiological pathways [OPG/RANKL (LGR4); Wnt-ß-catenin pathway], also affected in CKD, offers great opportunities to further unravel the complex physiopathology of CKD-MBD and to improve outcomes.

Vitamin D and Chronic Kidney Disease Association with Mineral and Bone Disorder: An Appraisal of Tangled Guidelines.

Chronic kidney disease (CKD) is a highly prevalent condition worldwide in which the kidneys lose many abilities, such as the regulation of vitamin D (VD) metabolism. Moreover, people with CKD are at a higher risk of multifactorial VD deficiency, which has been extensively associated with poor outcomes, including bone disease, cardiovascular disease, and higher mortality. Evidence is abundant in terms of the association of negative outcomes with low levels of VD, but recent studies have lowered previous high expectations regarding the beneficial effects of VD supplementation in the general population. Although controversies still exist, the diagnosis and treatment of VD have not been excluded from nephrology guidelines, and much data still supports VD supplementation in CKD patients. In this narrative review, we briefly summarize evolving controversies and useful clinical approaches, underscoring that the adverse effects of VD derivatives must be balanced against the need for effective prevention of progressive and severe secondary hyperparathyroidism. Guidelines vary, but there seems to be general agreement that VD deficiency should be avoided in CKD patients, and it is likely that one should not wait until severe SHPT is present before cautiously starting VD derivatives. Furthermore, it is emphasized that the goal should not be the complete normalization of parathyroid hormone (PTH) levels. New developments may help us to better define optimal VD and PTH at different CKD stages, but large trials are still needed to confirm that VD and precise control of these and other CKD-MBD biomarkers are unequivocally related to improved hard outcomes in this population.

Creatine Kinase Elevation in Autosomal Dominant Polycystic Kidney Disease Patients on Tolvaptan Treatment.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cause of end-stage kidney disease. Currently, tolvaptan is the only treatment that has proven to delay disease progression. The most notable side effect of this therapy is drug-induced liver injury; however, recently, there have been two reports of creatine kinase (CK) elevation in ADPKD patients on tolvaptan treatment. We set out to monitor and determine the actual incidence of CK elevation and evaluate its potential association with other clinical factors. METHODS: This is an observational retrospective multicenter study performed in rapidly progressive ADPKD patients on tolvaptan treatment from Barcelona, Spain. Laboratory tests, demographics, treatment dose, and reported symptoms were collected from October 2018 to March 2021. RESULTS: Ninety-five patients initiated tolvaptan treatment during follow-up. The medication had to be discontinued in 31 (32.6%) patients, primarily due to aquaretic effects (12.6%), elevated liver enzymes (8.4%), and symptomatic or persistently elevated CK levels (3.2%). Moreover, a total of 27 (28.4%) patients had elevated CK levels, with most of them being either transient (12.6%), mild and asymptomatic (4.2%), or resolved after dose reduction (3.2%) or temporary discontinuation (2.1%). CONCLUSION: We pre-sent the largest cohort that has monitored CK levels in a real-life setting, finding them elevated in 28.4% of patients. More research and monitoring will help us understand the clinical implications and the pathophysiological mechanism of CK elevation in this population.

Los riñones también hablan español / Kidneys also speak Spanish

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Evidence in chronic kidney disease-mineral and bone disorder guidelines: is it time to treat or time to wait?

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is one of the many important complications associated with CKD and may at least partially explain the extremely high morbidity and mortality among CKD patients. The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline document was based on the best information available at that time and was designed not only to provide information but also to assist in decision-making. In addition to the international KDIGO Work Group, which included worldwide experts, an independent Evidence Review Team was assembled to ensure rigorous review and grading of the existing evidence. Based on the evidence from new clinical trials, an updated Clinical Practice Guideline was published in 2017. In this review, we focus on the conceptual and practical evolution of clinical guidelines (from eMinence-based medicine to eVidence-based medicine and 'living' guidelines), highlight some of the current important CKD-MBD-related changes, and underline the poor or extremely poor level of evidence present in those guidelines (as well as in other areas of nephrology). Finally, we emphasize the importance of individualization of treatments and shared decision-making (based on important ethical considerations and the 'best available evidence'), which may prove useful in the face of the uncertainty over the decision whether 'to treat' or 'to wait'.

Osteoporosis, densidad mineral ósea y complejo CKD-MBD (II): implicaciones terapéuticas / Osteoporosis, bone mineral density and CKD-MBD (II): Therapeutic implications

La osteoporosis (OP) y la enfermedad renal crónica (ERC) influyen independientemente en la salud ósea. Numerosos pacientes con ERC presentan una disminución de densidad mineral ósea (DMO), un elevado riesgo de fracturas por fragilidad ósea y un incremento de su morbimortalidad. Con el envejecimiento de la población estos hechos no son dependientes solo de la «osteodistrofia renal» sino también de la OP asociada. Dado que la DMO tiene capacidad predictiva en pacientes con ERC (parte I), ahora analizaremos las implicaciones terapéuticas derivadas. Análisis post hoc de estudios aleatorizados han mostrado que fármacos como alendronato, risedronato, raloxifeno, teriparatida o denosumab tienen una eficacia comparable a la población general en pacientes con una disminución leve-moderada del filtrado glomerular (especialmente ERC-3). Estos estudios tienen limitaciones, pues incluyen mayoritariamente mujeres "sanas", sin diagnóstico conocido de ERC y habitualmente con parámetros normales de laboratorio; sin embargo, también existen datos positivos preliminares en estadios más avanzados (ERC-4) y más limitados en ERC-5D. Por todo ello, al menos en ausencia de alteraciones significativas del metabolismo mineral (i.e., hiperparatiroidismo severo), el beneficio potencial de dichos fármacos debería ser considerado en pacientes que presenten un riesgo de fractura elevado o muy elevado. Es novedad importante que las nuevas guías no condicionan su uso a la práctica de una biopsia ósea previa y que el beneficio/riesgo de estos fármacos podría estar justificado. Sin embargo, debemos considerar que la mayoría de estudios no son consistentes y tienen un bajo grado de evidencia, por lo que la indicación farmacológica (riesgo/beneficio) debe ser individualizada y prudente

Osteoporosis (OP) and chronic kidney disease (CKD) both independently affect bone health. A significant number of patients with CKD have decreased bone mineral density (BMD), are at high risk of fragility fractures and have an increased morbidity and mortality risk. With an ageing population, these observations are not only dependent on "renal osteodystrophy" but also on the associated OP. As BMD predicts incident fractures in CKD patients (part I), we now aim to analyse the potential therapeutic consequences. Post-hoc analyses of randomised studies have shown that the efficacy of drugs such as alendronate, risedronate, raloxifene, teriparatide and denosumab is similar to that of the general population in patients with a mild/moderate decline in their glomerular filtration rate (especially CKD-3). These studies have some flaws however, as they included mostly "healthy" women with no known diagnosis of CKD and generally with normal lab test results. Nevertheless, there are also some positive preliminary data in more advanced stages (CKD-4), even though in CKD-5D they are more limited. Therefore, at least in the absence of significant mineral metabolism disorders (i.e. severe hyperparathyroidism), the potential benefit of these drugs should be considered in patients with a high or very high fracture risk. It is an important change that the new guidelines do not make it a requirement to first perform a bone biopsy and that the risk/benefit ratio of these drugs may be justified. However, we must also be aware that most studies are not consistent and the level of evidence is low. Consequently, any pharmacological intervention (risk/benefit) should be prudent and individualized

Osteoporosis, bone mineral density and CKD-MBD (II): Therapeutic implications. / Osteoporosis, densidad mineral ósea y complejo CKD-MBD (II): implicaciones terapéuticas.

Osteoporosis (OP) and chronic kidney disease (CKD) both independently affect bone health. A significant number of patients with CKD have decreased bone mineral density (BMD), are at high risk of fragility fractures and have an increased morbidity and mortality risk. With an ageing population, these observations are not only dependent on "renal osteodystrophy" but also on the associated OP. As BMD predicts incident fractures in CKD patients (partI), we now aim to analyse the potential therapeutic consequences. Post-hoc analyses of randomised studies have shown that the efficacy of drugs such as alendronate, risedronate, raloxifene, teriparatide and denosumab is similar to that of the general population in patients with a mild/moderate decline in their glomerular filtration rate (especially CKD-3). These studies have some flaws however, as they included mostly "healthy" women with no known diagnosis of CKD and generally with normal lab test results. Nevertheless, there are also some positive preliminary data in more advanced stages (CKD-4), even though in CKD-5D they are more limited. Therefore, at least in the absence of significant mineral metabolism disorders (i.e. severe hyperparathyroidism), the potential benefit of these drugs should be considered in patients with a high or very high fracture risk. It is an important change that the new guidelines do not make it a requirement to first perform a bone biopsy and that the risk/benefit ratio of these drugs may be justified. However, we must also be aware that most studies are not consistent and the level of evidence is low. Consequently, any pharmacological intervention (risk/benefit) should be prudent and individualised.

Valores Espirométricos en Estudiantes de Medicina de la Universidad Mayor de San Simón (Junio-Diciembre 2009) / Spirometric Data in Medical Students from Mayor the San Simon University (June-December 2009)

Introducción: Los valores espirométricos constituyen un test de detección invaluable de salud del aparato respiratorio e identifican individuos en riesgo de enfermedad pulmonar, por tanto es importante establecer valores de referencia de cada comunidad. Objetivos: Determinar los valores del Flujo Espiratorio Máximo (FEM) yVolumen Espiratorio Forzado en el primer segundo (FEV-1) en estudiantes de la Facultad de Medicina de la Universidad Mayor de San Simón, período Junio - Diciembre 2009; además determinar valores promedio de FEM en estudiantes que fuman y no fuman, realizan deporte y aquellos que no, y estudiantes sanos o con patología pulmonar y/o cardíaca. Materiales y métodos: Estudio descriptivo, prospectivo y longitudinal. Muestra 221 estudiantes (18 a 25 años). Se utilizó la técnica de medición preestablecida internacionalmente empleando un espirómetro manual. Los datos se recolectaron en una hoja de registro y el análisis estadístico (t-Student y correlación) se realizó en SPSS. Resultados: Los valores promedio de FEM en L/min fueron: 517,28± 145,19 en personas sanas, 421,42± 156,04 en personas con patología pulmonar y/o cardíaca (p<0,001);en personas fumadoras 523,74± 151,03, en no fumadores 426,3 1 ± 154,81 (p<0,001); entre personas deportistas 466,72± 160 y 424,86± 155,61 en no deportistas (p=0,071). Los valores promedio de FEV-1 en L/seg fueron:varones 3,39 (18-20 años) y 3,76 (21-25 años), mujeres 2,79 (18-20 años) y 2,72 (21-25 años). Conclusión: Los valores de FEM y FEV-1 son inferiores a valores internacionales, y están en relación directa con la estatura. Las personas sanas, fumadoras poseen un valor de FEM más alto.

Background: Spirometric values are an invaluable test of health screening of the respiratory and identifying individuals at risk for lung disease, it is therefore important to establish reference values of each community. Objectives: To determine the values of peak expiratory flow (PEF) and Forced Expiratory Volume in one second (FEV-1) students of the Faculty of Medicine of the Universidad Mayor de San Simón, period June-December 2009; also determine average values FEM in students who smoke and nonsmokers, and those who do physical exercise and students not healthy or lung disease and / or heart disease. Materials and methods: In this prospective, longitudinal study. Sample 221 students (18-25 years).We used the preset measurement technique using a spirometer internationally Microlife ® manual. Data were collected on a log sheet and statistical analysis (t-Student and correlation) was performed in SPSS. Results: The mean values of PEF in L / min were 517,28 ± 145,19 in healthy subjects, 421,42 ± 156,04 in people with lung disease and / or heart rate (p = 0,00) in people smokers and 523,74 ± 151,03 426,31 ± 154,81 in nonsmokers (p = 0,00) and between people and athletes 466,72 ± 160 424,86 ± 155,61 in non-athletes (p = 0,071) The average values of FEV-1 in L / sec were: 3,39 male (18-20 years) and 3,76 (21 -25 years), women 2,79 (18-20 years) and 2,72 (21 -25 years). Conclusion: The values of PEF and FEV-1 are lower than international values, and are in direct relation to height. Healthy people, smokers have a higher PEF value.

Liposarcoma Retroperitoneal Gigante: A Propósito de un Caso / Giant Retroperitoneal Liposarcoma: On Purpose of a Case

Los tumores retroperitoneales representan un 0,07 a 0,2% de todas las neoplasias del organismo. Los liposarcomas, formas predominantes de sarcomas, se originan del mesodermo embrionario y pueden alcanzar grandes dimensiones en el retroperitoneo, presentándose en forma de masas voluminosas sin sintomatología específica. Las metástasis a distancia son poco probables; la mortalidad específica es del 40 al 50% a los 5 años del diagnóstico y su pronóstico depende de su variedad histopatológica. La conducta es quirúrgica y consiste en exéresis radical del tumor; junto con la radioterapia y la quimioterapia como tratamiento paliativo. Se presenta un caso del liposarcoma retroperitoneal gigante bien diferenciado de células fusiformes; manifestado por distensión abdominal progresiva acompañado de dolor tipo opresivo de moderada intensidad y el tratamiento efectuado, la resección quirúrgica radical.

The retroperitoneal tumors represent 0.07 to 0.2% of all neoplasias.The liposarcomas are predominant forms of sarcomas, they can reach big size in the retroperitoneum, and they show like voluminous mass without specific symptomatology. The metastasis is improbable; the specific mortality is from 40 to 50% in 5 years since the diagnostic, and the prognostic depends of the histopathologic variety. The conduct is surgical and this consists in radical excision of the tumor, together with radiotherapy and chemotherapy, like palliative treatments. We present a case of giant retroperitoneal liposarcoma, differentiated of fusiforms cells; it is shown as a progressive abdominal distension with oppressive pain of moderate intensity; and the treatment effectuated was the radical surgical excision.