Myocardial work in chronic kidney disease: insights from the CPH-CKD ECHO Study.

BACKGROUND: Myocardial work is a novel echocardiographic measure that offers detailed insights into cardiac mechanics. We sought to characterize cardiac function by myocardial work in patients with chronic kidney disease (CKD). METHODS: We prospectively enrolled 757 patients with non-dialysis-dependent CKD and 174 age- and sex-matched controls. Echocardiographic pressure-strain loop analysis was performed to acquire the global work index (GWI). Linear regressions were performed to investigate the association between estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) to GWI. RESULTS: Patients with CKD had a mean age of 57 years, 61% were men, and median eGFR was 42 mL/min/1.73 m2. Overall, no difference in GWI was observed between patients and controls (1879 vs. 1943 mmHg%, p = 0.06). However, a stepwise decline in GWI was observed for controls vs. patients with CKD without left ventricular hypertrophy vs. patients with CKD and left ventricular hypertrophy (GWI, 1943 vs. 1887 vs. 1789 mmHg%; p for trend = 0.030). In patients with CKD, eGFR was not associated with GWI by linear regression. However, diabetes modified this association (p for interaction = 0.007), such that per 10 mL/min/1.73 m2 decrease in eGFR, GWI decreased by 22 (9-35) mmHg% (p = 0.001) after multivariable adjustments in patients without diabetes, but with no association between eGFR and GWI in patients with diabetes. No association was observed between UACR and GWI. CONCLUSION: Patients with CKD and left ventricular hypertrophy exhibited lower myocardial work compared to matched controls. Furthermore, decreasing eGFR was associated with decreasing myocardial work only in patients without diabetes. No association to UACR was observed.

Diurnal blood pressure patterns and the relationship between kidney function and bedrest blood pressure in athletes

The focus of this study is to explore the regulation of blood pressure (BP), its diurnal rhythm, and the association with renal impairment in athletes with chronic kidney disease. Given the high physical demands and unique physiological stressors faced by athletes, understanding these dynamics is crucial. The study categorized chronic kidney disease patients treated at our hospital into three groups based on their BP rhythm: dipper BP, non-dipper BP, and anti-dipper BP. A retrospective analysis was conducted on the general condition of these patients and their bedrest BP values, examining correlations with kidney function. Findings revealed significant differences in diurnal diastolic BP (dDBP), nocturnal systolic BP (nSBP), and nocturnal pulse pressure variation (P<0.05). The study concludes that most athletes with chronic nephropathy exhibit non-dipper and anti-dipper BP rhythms. Notably, abnormal diurnal BP patterns, elevated nocturnal pulse pressure variation, and high diastolic BP were all linked to renal impairment. These findings suggest that bedrest BP provides comprehensive insights into an athlete's BP profile, aiding in targeted treatments to slow kidney function decline and reduce the risk of cardiovascular and cerebrovascular events. Understanding these patterns is essential for optimizing the health and performance of athletes managing chronic nephropathy (AU)

Metformin, chronic nephropathy and lactic acidosis: a multi-faceted issue for the nephrologist.

Metformin is currently considered a first-line therapy in type 2 diabetic patients. After issuing warnings for decades about the risks of lactic acidosis in patients with chronic nephropathy, metformin is now being re-evaluated. The most recent evidence from the literature has demonstrated both a low, acceptable risk of lactic acidosis and a series of favorable effects, which go beyond its hypoglycemic activity. Patients treated with metformin show a significant mortality reduction and lower progression towards end-stage renal disease in comparison with those treated with other hypoglycemic drugs. Concerning lactic acidosis, in the last few years it has been shown how lactic acidosis almost always developed when patients kept taking the drug in the face of a concomitant disease or situation such as sepsis, fever, diarrhea, vomiting, which reduced metformin renal clearance. Actually, clearance of metformin is mainly renal, both by glomerular filtration and tubular secretion (apparent clearance 933-1317 ml/min, half-life < 3 h). As regards treatment, in cases of lactic acidosis complicated by acute kidney injury, continuous renal replacement therapy (CRRT) plays a crucial role. Besides the elimination of metformin, CRRT  improves survival by correcting acidosis, electrolyte alterations, and maintaining fluid balance. Lactic acidosis almost always develops because of preventable drug accumulation. Therefore, prevention is a key factor. Patients should be aware that discontinuation for a limited time does not affect their health, even when it may be inappropriate, but it may avoid a serious, potentially fatal adverse event.

Comparative metabolism of two major compounds in Fructus Corni extracts by gut microflora from normal and chronic nephropathy rats in vitro by UPLC-Q-TOF/MS.

Herbal medicines are widely used as therapeutic products in many countries. Fructus Corni, a traditional herb medicine, has been clinically used to cure chronic nephropathy for thousands of years. It could be converted by gut microflora in vivo to shape its pharmacological profiles. Thus, metabolic profiles of major active constituents in Fructus Corni extracts by gut microflora from rats in healthy and nephropathy state were firstly investigated in vitro by ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) in this study. According to the features of protonated ions, five metabolites (M1, M2, M3, M5 and M6) were found and preliminarily authenticated. Intestinal bacteria were capable of converting N0 (loganin) to its aglycone M1 (loganetin). The latter was further hydrogenated to the corresponding M2 (hydrogenated loganetin) and subsequently to M3 (hydrogenated and demethylated loganetin) by demethylation; While M5 (demethylated morronisid aglycone) and M6 (dehydroxylated morronisid aglycone) were identified as the two metabolites of N4 (morronisid) through demethylation and dehydroxylation. Gut microflora from healthy and nephropathy rats could degrade loganin and morronisid to the above metabolites. However, healthy rat intestinal bacteria showed more powerful degradation and much more amounts of M1 and M6 were obtained in their samples. Additionally, this work demonstrated that UPLC-Q-TOF/MS approach connected with MetaboLynx™ analysis software was rapid and reliable for screening and authentication of natural product metabolites.

Causal mechanism and component causes in Mesoamerican-Sri Lankan nephropathy: the moderator's view.

Inspired by Conan Doyle's novels, the pro contender of this Polar View undertakes an elegant exercise in territory common to epidemiology and police investigation and concludes that cyclic episodes of dehydration in individuals exposed to heavy work in very hot climates is the cause of Mesoamerican and Sri Lankan nephropathy. The contender in the opposite camp accepts the idea that dehydration may play a key role in this condition but highlights a different explanation, that it is contaminated water used for rehydration that is the eventual cause of the disease.Causal mechanisms result from the combination of many components, i.e. conditions or events that are needed for the occurrence of the disease. If we adopt a global, extended approach to the problem, it is unlikely that cyclic dehydration is a key component in all cases. While credible in most cases in Central America, the cyclic dehydration hypothesis fails to explain most cases in Sri Lanka, where agrochemicals have been implicated as the most likely cause of this disease. The experience with Balkan nephropathy is an enduring lesson that full clarification of the causal mechanisms behind endemic nephropathies can be a decades-long process. Therefore, action to control Mesoamerican and Sri Lankan nephropathy should not be deferred. Deployable interventions include the provision of uncontaminated water sources, prevention of dehydration at work sites and the application of safety procedures for agrochemicals. The joint application of these interventions will most likely benefit the populations plagued by this endemic disease.

Achieving remission of proteinuria in childhood CKD.

BACKGROUND: A multidrug treatment strategy that targets urinary proteins with an angiotensin-converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) up-titrated to the respective maximum tolerated dose combined with intensified blood pressure (BP) control has been found to prevent renal function loss in adults with proteinuric nephropathies. Herein, we investigated the effects of this treatment protocol in the pediatric patient population. METHODS: From May 2002 to September 2014 we included in this observational, longitudinal, cohort study 20 consecutive children with chronic nephropathies and 24-h proteinuria of >200 mg who had received ramipril and losartan up-titrated to the respective maximum approved and tolerated doses [mean (standard deviation) dose:2.48 (1.37) mg/m2 and 0.61 (0.46) mg/kg daily, respectively]. The primary efficacy endpoint was a >50 % reduction in 24-h proteinuria to <200 mg (remission). Secondary outcomes included changes in proteinuria, serum albumin, BP, and glomerular filtration rate (GFR). RESULTS: Mean (± standard deviation) patient age at inclusion was 13.8 ± 2.8 years, and the median [interquartile range (IQR)] serum creatinine level and proteinuria were 0.7 (0.6-1.0) mg/dl and 690 (379-1270) mg/24 h or 435 (252-711) mg/m2/24 h, respectively. Proteinuria significantly decreased by month 6 of follow-up, and serum albumin levels increased over a median follow-up period of 78 (IQR 39-105) months. In the nine children who achieved remission, proteinuria reduction persisted throughout the whole follow-up without rebounds. The GFR improved in those children who achieved remission and worsened in those who did not. The mean GFR slopes differed significantly between these two groups (p < 0.05), being positive in those children with remission and negative in those without remission (+0.023 ± 0.15 vs.-0.014 ± 0.23 ml/min/1.73 m2/month, respectively), whereas BP control was similar between the two groups. Hyperkalemia was observed in two children. CONCLUSIONS: Combination therapy with maximum approved doses of ACE inhibitors and ARBs is a safe strategy which may achieve proteinuria remission with kidney function stabilization or even improvement in a substantial proportion of children with proteinuric nephropathies.

Study on the expression levels of connective tissue growth factor and hepatocyte growth factor in serum of patients with nephropathy and renal fibrosis and the clinical significance / 国际检验医学杂志

Objective To investigate the expression levels of connective tissue growth factor(CTGF)and hepatocyte growth fac-tor(HGF)in the serum of patients with nephropathy and the relationship with renal fibrosis.Methods Levels of serum CTGF, HGF,blood urea nitrogen(BUN),creatinine(Cr)and Cystatin C(SCys C)in 87 patients with chronic nephropathy and 40 healthy persons(control group)were determined by enzyme-linked immunosorbent assay(ELISA)and the automatic biochemical analyzer. The correlation of indexes like serum CTGF with glomerular sclerosis and renal tubule interstitial fibrosis score in patients with chronic nephropathy was analyzed by Pearson correlation analysis.Results The levels of serum BUN,Cr and Cys-C and in patients with grade Ⅲ and grade Ⅳ chronic nephropathy were significantly higher than those in the control group(P<0.05).The levels of serum CTGF and HGF in patients with grade Ⅱ,grade Ⅲ and grade Ⅳ chronic nephropathy were significantly higher than those in the control group(P<0.05).For patients with gradeⅢ - Ⅳ chronic nephropathy,the levels of Cys-C and serum CTGF increased with the increase of grade(P<0.05).Pearson correlation analysis showed that serum CTGF,HGF,BUN,Cr and Cys-C were signif-icantly positively correlated with glomerular sclerosis score and renal tubule interstitial fibrosis score(P<0.05).Conclusion Serum CTGF and HGF may be involved in the occurrence and renal fibrosis of chronic nephropathy.

How to differentiate renal senescence from chronic kidney disease in clinical practice.

Renal aging is frequently confused with chronic nephropathy in clinical practice, since there are some similarities between them, particularly regarding reduced glomerular filtration rate (GFR). However, there are many differences between these two entities which can help any practitioner to distinguish between them, such as: GFR deterioration rate, hematocrit, renal handling of urea, creatinine and some electrolytes, tubular acidification, urinalysis, and renal imaging. Differentiation between renal aging and chronic renal disease is crucial in order to avoid unnecessary medicalization of what is a physiological change associated with the healthy aging process, and the potential harmful consequences of such overdiagnosis. A recently described equation (HUGE), as well as an adequate nephrological evaluation and follow up can help physicians to distinguish both entities.

Nephroprevention in the oldest old with chronic kidney disease: Special considerations.

Nephroprevention strategies are crucial for handling chronic kidney disease (CKD) complications, and slowing its progression. However, these preventative measures should be guided by major geriatrics principles in order to help nephrologists to adequately handle the oldest old with CKD. These geriatric concepts consist of taking into account the relevance of choosing an individualized therapy, handling clinical frailty, and keeping a geriatric perspective which means that a good quality of life is sometimes a more important therapeutic objective in octogenarians than merely prolonging life. Even though nephroprevention strategies for treating the oldest old with CKD are basically similar to those applied to younger patients such as low sodium and protein diet, optimized hemoglobin levels, blood pressure and metabolic control, the treating physician or care provider must at all times be ready to make fundamental adjustments and tweak patient care paradigms and objectives if and when the initial therapeutic options applied have caused unintended clinical consequences and complications. Additionally, the sarcopenia status should also be evaluated and treated in very old CKD patients.

Intervention mechanisms of Chinese materia medica on inflammatory injury of renal tissue with chronic nephropathy / 中草药

Chronic kidney disease is closely related to inflammation. Chinese materia medica (CMM) or their extracts can intervene in some signal transduction paths such as nuclear factor-kappa B (NF-κB) path, mitogen activated protein kinase (MAPK) path, Toll-like receptor 4 (TLR4) path, and regulate cytokines, adhesion molecules, transcription factors, acceptor molecules, and enzyme molecules to resist inflammatory injury of renal tissue from multiple target points. Because of the interaction, network, and magnification of inflammatory injury factors, the action of CMM shows the characteristics, such as multi-point, pleiotropy, overlap, and so on. The target points of CMM on inflammatory injury are explored and their molecular mechanism plays an important role in the prevention and control of chronic kidney disease and study on new drug.

Seguimiento del perfil proteico urinario en el trasplante renal / Follow-up of urine protein profile in renal transplant

La nefropatía crónica del trasplante (NCT) se caracteriza por fibrosis intersticial y atrofia tubular, pero su etiología es diversa. El objetivo del trabajo fue evaluar el seguimiento cualitativo de proteínas urinarias en pacientes con más de seis años de trasplante renal y compararlo con parámetros de laboratorio y con biopsia renal. Se evaluaron 17 pacientes durante un año, a través de creatinina sérica, proteinuria y fraccionamiento proteico por electroforesis en geles de poliacrilamida (SDS-PAGE) en una y dos dimensiones con coloración argéntica. Todos los pacientes con biopsias características de nefropatía crónica del trasplante presentaron un perfil tubular y aquellos con glomerulopatía del trasplante evidenciaron un perfil predominantemente glomerular. Los cambios en el perfil tubular se asociaron a infecciones urinarias, pulmonares e intestinales y a una respuesta inmunológica en el límite al rechazo (borderline), aún sin modificaciones evidentes en la creatinina sérica ni en la proteinuria. La electroforesis bidimensional permitió detectar claramente las proteínas orosomucoide y zinc alfa-2 glicoproteína, aparentemente asociadas a hialinosis arteriolar por toxicidad causada por ciclosporina. La electroforesis SDS-PAGE permitió identificar el sitio de lesión en el nefrón y cambios en la evolución, aún en presencia de vestigios de proteinuria. Las electroforesis SDS-PAGE mono y bidimensional se plantean como complemento para la evaluación de la condición clínica del paciente trasplantado renal crónico.

Post-transplant chronic nephropathy is characterized by interstitial fibrosis and tubular atrophy. These alterations are non-specific, but the glomerular and vascular lesions help to differentiate the etiological causes. The aim of this study was to determine the qualitative follow-up study of urine proteins in patients, six years after receiving a renal transplant, and compare their relationship to laboratory parameters and renal biopsy. The evolution of 17 patients with renal transplant was studied for one year, through serum creatinine, proteinuria, and polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate (SDS-PAGE) in one and two dimensions with silver staining. The patients with chronic nephropathy by renal biopsy presented a tubular profile of urinary proteins, and those who presented glomerulopathy showed a predominant glomerular profile. Changes in the tubular profiles during the follow-up study were associated to urinary tract, pulmonary, and intestinal infections, as well as borderline rejection, even without evident changes in either proteinuria or serum creatinine. The bidimensional electrophoresis clearly marked the orosomucoid proteins and zinc alpha-2 glycoprotein, generally associated to arterial hyalinosis due to ciclosporin toxicity. Even with traces of proteinuria, SDS-PAGE with silver staining made it possible to identify the renal lesion location. It also enabled the detection of the stable profiles of urinary proteins and changes in the evolution, without modification of serum creatinine. SDS-PAGE in one and two dimensions is used as a complement in the evaluation of renal transplant patients' clinical condition.

Prevención y tratamiento de la enfermedad renal crónica (ERC) / Recognition and prevention of chronic kidney disease (CKD)

La enfermedad renal crónica (ERC) es un grave problema de salud pública. Se espera que el número de personas con insuficiencia renal que reciben tratamiento con diálisis y trasplante aumente dramáticamente en los próximos años. Los malos resultados de la ERC no se limitan a la insuficiencia renal terminal, sino que también incluyen a las complicaciones derivadas de una menor función renal, como hipertensión arterial, anemia, desnutrición, trastornos óseos y minerales, neuropatía, así como un mayor riesgo de enfermedad cardiovascular. El diagnóstico precoz basado en la presencia de proteinuria o una velocidad de filtración glomerular estimada reducida, puede permitir la intervención temprana para reducir: el riesgo de insuficiencia renal progresiva, los eventos cardiovasculares y la mortalidad que se asocian con la ERC. Las estrategias eficaces para frenar la progresión de la ERC y reducir el riesgo cardiovascular están disponibles en la actualidad. Los modelos clínicos de atención que faciliten la entrega de los aspectos diversos y complejos del tratamiento en forma simultánea, podrían mejorar la gestión y probablemente los resultados clínicos

Chronic kidney disease (CKD) is a serious public health problem. The number of persons with kidney failure who are treated with dialysis and transplantation is expected to rise dramatically in the coming years. The poor outcomes of CKD are not restricted to kidney failure but also include the complications of decreased kidney function, such as hypertension, anemia, malnutrition, bone and mineral disorders and neuropathy, as well as increased risk of cardiovascular disease. Early diagnosis on the basis of presence of proteinuria or reduced estimated glomerular filtration rate could permit early intervention to reduce the risk of: kidney failure, cardiovascular events and death that are associated with CKD. Effective strategies are available to slow the progression of CKD and reduce cardiovascular risk. Clinical models of care that facilitate delivery of the many complex aspects of treatment simultaneously could enhance management and probably the clinical outcomes

Escore de condição corporal como indicador do prognóstico de gatos com doença renal crônica / Body condition score as an indicator of prognosis for cats with chronic renal disease

A caquexia tem sido relacionada à maior mortalidade de pacientes com doença renal crônica, tanto em humanos, como em animais. O escore de condição corporal (ECC) pode ser utilizado em conjunto com o peso para melhor avaliação da composição corporal desses animais. O objetivo deste trabalho foi de correlacionar o escore de condição corporal com o prognóstico de felinos com doença renal crônica. Avaliaram-se 110 felinos idosos, dos quais 70 apresentavam-se hígidos (Grupo I) e 40 apresentavam doença renal crônica (Grupo II). No grupo I, apenas 5,7 por cento dos gatos apresentaram ECC abaixo do ideal e destes nenhum foi classificado como caquético. No grupo II, 70 por cento dos gatos apresentaram ECC abaixo do ideal, dos quais 32,5 por cento eram caquéticos. A taxa de mortalidade no grupo II foi significantemente maior naqueles caquéticos. O ECC abaixo do considerado ideal indica um prognóstico desfavorável nos pacientes com doença renal crônica.

Cachexia has been associated with higher mortality in patients with chronic renal disease both in human and veterinary medicine. Body condition score (BCS) can be used along with body weight for a better evaluation of a patient's body composition. The objective of this study was to associate body condition score with prognosis of cats with chronic renal disease. One hundred and ten elderly cats were evaluated; of which 70 were healthy (Group I) and 40 had been diagnosed with chronic renal disease (Group II). In Group I, only 5.7 percent of the cats presented a BCS below ideal, though none were found to be cachectic. In Group II, 70 percent of the cats presented a BCS below ideal, where 32.5 percent were cachectic. Mortality was significantly higher within the cachectic patients of Group II. BCS below ideal indicates a poor prognosis for patients with chronic renal disease.

Efectos crónicos y tratamiento con litio sobre la anatomía y función renal / Chronic effects of lithium treatment in renal anatomy and function

Lithium is a drug widely used in clinical psychiatry, often as first-line treatment. However, it has generated much controversy because of the likely adverse effects of both acute and chronic use, mainly in the kidney. With respect to prolonged exposure to lithium, it would be detrimental to the kidneys at variable extent, depending on factors such as duration of treatment, dosage of drug, patient age, renal damage, prior comorbidities, among others not yet sufficiently elucidated. The principal mechanism of renal function changes was determined by morphological changes, such as interstitial nephritis, interstitial-medullar fibrosis and tubular atrophy, all irreversible phenomena that ultimately lead to a tubuloglomerular imbalance and commitment of the GFR. Other aspects of chronic nephropathy induced by lithium and their production mechanisms are being studied, also the search and advanced diagnostic techniques to predict and / or detect early changes. Among them have described the pathology (renal biopsy), although this form of diagnosis is very late. Thus it seeks the introduction of imaging and serological markers of kidney failure as tools that provide information about kidney condition earlier.

El Litio es un fármaco ampliamente utilizado en psiquiatría, muchas veces como tratamiento de primera línea. Existe en la actualidad una activa controversia acerca de sus probables efectos adversos a nivel renal, tanto agudos como crónicos, ya que la exposición prolongada al Litio sería deletérea para el riñón en una magnitud variable, dependiendo de factores como duración del tratamiento, dosis del fármaco, edad del paciente, daño renal previo y comorbilidad, entre otros aún no suficientemente dilucidados. El origen del mecanismo principal de alteración de la función renal estaría en alteraciones morfológicas como la Nefritis Intersticial, la Fibrosis Intersticio-Medular y la Atrofia Tubular, todos fenómenos irreversibles que finalmente conducirían a un desbalance tubuloglomerular y a un compromiso de la VFG. Otros aspectos de la Neuropatía Crónica inducida por Litio y de sus mecanismos de producción se encuentran en estudio, así como también la búsqueda y perfeccionamiento de técnicas diagnósticas que permitan predeciry/o detectar tempranamente los cambios mencionados. Entre estas últimas se ha descrito la anatomía patológica (biopsia renal), aunque esta es una forma de diagnóstico muy tardía. Es por ello que se busca la introducción de la imagenología y de marcadores serológicos de falla renal como herramientas que entreguen información sobre la condición del riñón más precozmente.