Resilience to acute kidney injury in offspring of maternal protein restriction.

Protein restriction (PR) during pregnancy induces morphofunctional alterations related to deficient nephrogenesis. We studied the renal functional and morphological significance of PR during pregnancy and/or lactation in adult male rat offspring and the repercussions on acute kidney injury (AKI) severity. Female rats were randomly assigned to the following groups: control diet during pregnancy and lactation (CC), control diet during pregnancy and PR diet during lactation (CR), PR during pregnancy and control diet during lactation (RC), and PR during pregnancy and lactation (RR). Three months after birth, at least 12 male offspring of each group randomly underwent either bilateral renal ischemia for 45 min [ischemia-reperfusion (IR)] or sham surgery. Thus, eight groups were studied 24 h after reperfusion: CC, CC + IR, CR, CR + IR, RC, RC + IR, RR, and RR + IR. Under basal conditions, the CR, RC, and RR groups exhibited a significant reduction in nephron number that was associated with a reduction in renal blood flow. Glomerular hyperfiltration was present as a compensatory mechanism to maintain normal renal function. mRNA levels of several vasoactive, antioxidant, and anti-inflammatory molecules were decreased. After IR, renal function was similarly reduced in all of the studied groups. Although all of the offspring from maternal PR exhibited renal injury, the magnitude was lower in the RC and RR groups, which were associated with faster renal blood flow recovery, differential vasoactive factors, and hypoxia-inducible factor-1α signaling. Our results show that the offspring from maternal PR are resilient to AKI induced by IR that was associated with reduced tubular injury and a differential hemodynamic response.

Integrative View of the Mechanisms that Induce Acute Kidney Injury and its Transition to Chronic Kidney Disease.

There is ample evidence showing that acute kidney injury (AKI) increases the risk of developing chronic kidney disease (CKD). Although considerable efforts have been undertaken in recent years to elucidate the mechanisms responsible for the AKI to CKD transition, many questions remain to be answered. In this review, we address most of the latest studies elucidating the mechanisms involved in this transition. Based on recent studies, the consensus to date is that endothelial and proximal tubular epithelium injury along with the activation of inflammatory processes occurring after an AKI episode, not only establish a close interrelation but also trigger a series of signaling pathways that culminate in the generation of tubulointerstitial fibrosis and chronic hypoxia, which lead to the progressive deterioration of functional tissue. These events highlight that the tubular epithelium does not appear to be the same after cell damage occurs. In this review, we present the advances aimed at elucidating the mechanisms that lead to a maladaptive response and how sex hormones seem to be involved in a positive or negative adaptive response. Elucidating and characterizing the mechanisms responsible for the AKI to CKD transition are an indispensable preliminary step that will help to identify the most important actors in this process.

Atypical Red Blood Cells Are Prevalent in California Sea Lion Pups Born during Anomalous Sea Surface Temperature Events.

To date, there is limited knowledge of the effects that abnormal sea surface temperature (SST) can have on the physiology of neonate pinnipeds. However, maternal nutritional deficiencies driven by alimentary restrictions would expectedly impact pinniped development and fitness, as an adequate supply of nutrients is essential for growth and proper functioning of all body systems, including red blood cell synthesis and clearance. Here, we investigated red blood cell morphology of California sea lion (CSL) pups from the San Benito Archipelago born during the 2014 and 2015 anomalously high SST events recorded in the northeastern Pacific Ocean. We examined whether atypical erythrocyte morphologies were more common in 2015, when the high SST event was more pronounced, and whether the stable isotope signature of pup fur, as an indicator of maternal feeding strategies, accounted for the number of atypical cells. Various atypical erythrocyte morphologies were more prevalent and more abundant than reference values. Evidence of iron deficiency was found in both years, and only pups born in 2014 showed evidence of active erythropoiesis. Microcytes and reticulocytes were more common in pups with higher isotopic δ13C and lower δ15N values, suggesting a probable relationship between maternal feeding strategies and the effect of climatic anomalies on red blood cell physiology of their pups. As developing pinnipeds require increased oxygen storage capacity for diving and foraging, the presence of atypical erythrocytes could be relevant to CSL pup fitness if the underlying cause is not reverted. This study is a first step to explore the effects that climatic alterations in the marine environment can have on the blood physiology of developing individuals.

Pharmacokinetics and hematotoxicity of a novel copper-based anticancer agent: casiopeina III-Ea, after a single intravenous dose in rats.

Casiopeina III-Ea is a mixed chelate copper (II) complex that has shown cytotoxic and antitumor activity in vitro and in vivo. The aim of this study was to investigate the pharmacokinetics of total copper derived from casiopeina III-Ea administered by intravenous bolus injection to Wistar rats. Other objective was to evaluate the hematotoxicity produced by this compound in those animals. Wistar rats received a single intravenous dose of 4 mg/kg of casiopeina III-Ea. Blood samples were taken and pharmacokinetics evaluated. Furthermore, erythrocyte copper levels were determined to identify a potential target and Zn levels were analyzed to determine a possible change. For the evaluation of hematotoxicity, both blood and urine samples were collected for hematological and biochemical analyses; moreover, Fe determination was performed. Blood copper and zinc levels, red blood cell copper levels as well as copper, zinc, and iron amounts excreted into urine were analyzed by ICP-MS. The blood concentration-time profile of copper derived from casiopeina III-Ea was fitted to a two-compartment model with a zero-order input. Cumulative amounts of Cu, Zn, and Fe excreted into rat urine after administration of casiopeina III-Ea were different with respect to control. Hematological and biochemical data indicated a hemolytic toxicity. Pharmacokinetic analysis of total copper derived from casiopeina III-Ea provided a general knowledge about distribution and elimination process of this compound. Additionally, the systemic exposure of the copper derived from casiopeina III-Ea accounts for the hematotoxicity of this complex at test dose.

Informe de un caso de doble tracto de salida del ventrículo derecho e hipoplasia del ventrículo izquierdo en un perro / Double outlet right ventricle and left ventricle hypoplasia in a dog. A case report

Double outlet right ventricle (DORV) and left ventricle hypoplasia are congenital cardiac defects rarely described in the dog. It is characterized by the great vessels (pulmonary artery and aorta) originating from right ventricle, and the left ventricle lacking development. A clinical case of a four months old female Chihuahua puppy, with clinical history of depression, abnormal cardiac sounds and cyanosis is described. Hemogram, radiology and echocardiogram were performed. The patient died suddenly and the postmortem study revealed DORV and left ventricle hypoplasia. The objective of this report is to portray the clinical findings, hemodynamic changes and anatomopathological findings in this dog, to contribute to the knowledge of this congenital defect barely described in veterinary medicine.

El doble tracto de salida del ventrículo derecho (DTSVD) e hipoplasia del ventrículo izquierdo son enfermedades cardiacas congénitas escasamente descritas en el perro, se caracterizan por el origen de los grandes vasos (arteria pulmonar y aórtica) a partir del ventrículo derecho y desarrollo incompleto del ventrículo izquierdo. El caso clínico que se presenta corresponde a un perro, hembra, Chihuahueño, de 4 meses de edad con historia clínica de depresión, cianosis y sonidos cardiacos anormales. Se realizó hemograma, estudio radiográfico de silueta cardiaca y ecocardiograma. El animal murió súbitamente y en el estudio post mortem presentó DTSVD e hipoplasia del ventrículo izquierdo. El objetivo de este trabajo fue describir los hallazgos clínicos, hemodinámicos y anatomopatológicos que se presentaron en el perro, con el fin de contribuir al conocimiento de esta malformación congénita cardiaca escasamente descrita en medicina veterinaria.

Alteraciones de analitos séricos y de orina en perros diabéticos: Informe de 30 casos / Alterations of serum and urine analytes in diabetic dogs: 30 cases report

The objective of this study was to describe alterations in blood clinical biochemistry and urinalysis which enable to establish the diagnosis of diabetes mellitus in dogs. Thirty cases of diabetic dogs were analyzed. The inclusion criteria were the following: hyperglycemia above 14 mmol/L, glucosuria, urine density above 1.014 and polyuria-polydipsia. Dogs of different breeds, from 7 months to 14 years of age and both genders (73.3% females and 26.7% males) were studied. The most frequent biochemical alterations in blood serum were: hyperglycemia (100%), increased urea (46%) and creatinine (13%), increase of enzyme activities ALT (50%), AST (46%), alkaline phosphatase (56%), amylase (20%), creatine kinase (66%); hypercholesterolemia (66%), hyperglobulinemia (33%), hyperphosphoremia (33%), hyperkaliemia (43%), hyponatremia (16%), hypochloremia (46%), hypobicarbonatemia (50%), increased anion gap (53%), increased strong ion difference (30%), increased serum osmolality (23%) and hypertriglyceridemia (50%). The urine density was between 1.015 and 1.064, mean value of urine glucose 49 mmol/L. Urine ketone bodies were detected in 10% of all cases. Described alterations in clinical biochemistry are important for the diagnosis, clinical care, and prognosis of dogs with diabetes mellitus.

El objetivo de este estudio fue describir alteraciones en la bioquímica clínica sanguínea y en el urianálisis, con el fin de establecer un diagnóstico integral en perros con diabetes mellitus. Se analizaron 30 casos de perros diabéticos. Los criterios de inclusión fueron: hiperglucemia superior a 14 mmol/L, glucosuria, densidad urinaria superior a 1.014 y poliuria-polidipsia. Los perros fueron de diferentes razas, de siete meses a 14 años de edad y de ambos géneros (73.3% hembras y 26.7% machos). Las frecuencias de las principales alteraciones bioquímicas en suero fueron: hiperglucemia (100.0%), incremento en las concentraciones de urea (46%) y de creatinina (13%), incremento de la actividad de las enzimas ALT (50%), AST (46%), fosfatasa alcalina (56%), amilasa (20%), creatina cinasa (66%), hipercolestrolemia (66%), hiperglobulinemia (33%), hiperfosforemia (33%), hipercaliemia (43%), hiponatremia (16%), hipocloremia (46%), hipobicarbonatemia (50%), aumento de ácidos no volátiles (53%), incremento en la diferencia de iones fuertes (30%), hiperosmolalidad (23%) e hipertrigliceridemia (50%). La densidad urinaria osciló entre 1.015 y 1.064, la glucosuria presentó, en promedio, 49 mmol/L. En 10% de los casos se observó cetonuria. Las alteraciones descritas en la bioquímica clínica son importantes para el diagnóstico, manejo clínico y pronóstico de los perros con diabetes mellitus.

Enfermedad glomeruloquística en dos perros con insuficiencia renal / Glomerulocystic kidney disease in two dogs with renal failure

Two cases of glomerulocystic kidney disease (GCKD) are described in dogs with renal failure. The laboratory test of the two dogs showed renal hyperazotemia with secondary non-regenerative anemia, associated to chronic renal failure. Macroscopic kidney lesions in both dogs were similar: showing multiple small cysts with an average of 1 mm in diameter, mainly in the renal cortex. Histopathological examination of the kidneys in both dogs revealed dilatation in the filtration space and Bowman's capsule forming cysts with glomerular atrophy and mild to severe periglomerular and interstitial fibrosis. These findings suggest that cystic glomerular changes may be developed as a consequence of fibrosis, which could act by compressing the glomerulo-tubular junctions. There are few reported cases of GCKD in dogs prior to these two. It may be explained that this is only a sporadic entity, adding that it may well be mistaken with other similar renal cystic pathologies, linked or not to a renal failure; therefore, it should be included in the differential diagnoses. For the first time, this report gives a clinical-pathological description of two cases in dogs with GCKD in Mexico.

Se describen dos casos de enfermedad glomeruloquística renal (EGQR) en perros con insuficiencia renal. En los análisis de laboratorio de ambos animales se encontró hiperazotemia renal con anemia no regenerativa secundaria, asociada con insuficiencia renal crónica. Las lesiones macroscópicas en los riñones de dichos perros fueron similares: se observaron múltiples pequeños quistes de 1 mm de diámetro en promedio, localizados principalmente en la corteza renal. En el examen histopatológico de los riñones de ambos perros se observaron dilataciones del espacio de filtración y de la cápsula de Bowman formando quistes, con atrofia de los ovillos glomerulares, así como fibrosis periglomerular e intersticial de moderada a severa. Estos hallazgos sugieren que los cambios glomerulares quísticos se pueden desarrollar como consecuencia de la fibrosis, la cual pudiera ejercer efecto compresor de las uniones glomérulo-tubulares. En el ámbito mundial, en perros caseros existen muy pocos informes previos de EGQR, debido quizá a que realmente es una entidad esporádica, además de que pudiera confundirse con otras patologías renales quísticas parecidas, asociadas o no con insuficiencia renal, por ello debe incluirse dentro de los diagnósticos diferenciales. Este informe aporta la descripción clínico-patológica de dos casos de EGQR en perros, por primera vez en México.