Correlación de biomarcadores de función renal en el primer acercamiento diagnóstico de la enfermedad renal crónica en perros

RESUMEN Objetivo. Determinar la correlación de los biomarcadores de funcionamiento renal en la primera evaluación en perros con diferentes factores de riesgo identificados para desarrollar enfermedad renal crónica (ERC). Materiales y métodos. Se realizó un estudio descriptivo, prospectivo de casos y controles de 388 animales, divididos en cinco grupos: grupo control (GC), y cuatro grupos de perros potencialmente enfermos renales (pERC). Se analizaron historia clínica, examen físico, condición corporal (CC), hemograma, perfil bioquímico con dimetilaginina simétrica (SDMA), urianálisis, ratio proteinuria/creatininuria (UPC) y medición de presión arterial sistémica. Se utilizó estadística no paramétrica y los datos fueron expresados en medianas y percentiles; para la CC se utilizó Xi2. Para los biomarcadores se realizó correlación de Spearman. Resultados. Para SDMA y la creatinina sérica (CrS) se observó una correlación moderada para pERC (r=0.69, p<0.001). Se observaron diferencias significativas en las variables edad (p=0.002), y CC (p<0.001) entre el GC y los pERC. Los animales azotemia leve (CrS 125-250 μmol/L) y/o con un valor de SDMA de 18-35 μg/dL, con o sin proteinuria tuvieron una mayor probabilidad de presentar un incremento de SDMA cuando se presentó una CC por debajo de 5/9 (OR=3.55, p=0.005). Conclusiones. El SDMA es un biomarcador complementario útil en etapas preazotémicas y en estadios avanzados donde existen caquexia y sarcopenia. Los biomarcadores deben evaluarse en conjunto para tener perspectiva completa de la función renal en los animales con factores de riesgo para desarrollar ERC.

ABSTRACT Objective. To determine the correlation of kidney function biomarkers at the first evaluation in dogs with different risk factors identified for developing chronic kidney disease (CKD). Materials and methods. A descriptive, prospective study of cases and controls of 388 animals, divided into five groups: control group (CG), and four groups of potentially kidney-diseased dogs (pCKD) was carried out. Clinical history, physical examination, body condition score (BCS), complete blood count, biochemical profile with symmetrical dimethylarginine (SDMA), urinalysis, urine protein/creatinine ratio (UPC), and systemic blood pressure were analyzed. Non-parametric statistics were used, and data were expressed as medians and percentiles; for BCS, Xi2 was used. For biomarkers, Spearman's correlation was performed. Results. For SDMA and serum creatinine (sCr), a moderate correlation was observed for pCKD (r=0.69, p<0.001). Significant differences were observed in the variables age (p=0.002) and BCS (p<0.001) between the CG and the pCKD. Animals with mild azotemia (sCr 125-250 μmol/L) and/or with an SDMA value of 18-35 μm/dL, with or without proteinuria, had a greater probability of presenting an increase in SDMA when the BCS was below 5/9 (OR=3.55, p=0.005). Conclusions. SDMA is a useful complementary biomarker in pre-azotemic stages and advanced stages where there is cachexia and sarcopenia. Biomarkers must be evaluated together to have a complete perspective of renal function in animals with risk factors for developing CKD.

Evaluation of kidney injury through early markers in canine pyometra / Avaliação de lesão renal através de marcadores precoce em piometra canina

Fourteen female dogs diagnosed with pyometra were studied at three separate times: at diagnosis (T0) and 24 h (T1) and 10-15 days (T2) after ovariohysterectomy (OH). The means of the markers, symmetric dimethylarginine (SDMA) (17.71 to 26.54 µg/dL) and the urinary gamma-glutamyl transferase to creatinine ratio (uGGT/uCr) (1.06 to 2.62 U/mg), varied, showing an increase with time. Further, the elevation of gamma-glutamyl transferase (uGGT) (56.61 to 128.12 U/L) and the urinary protein to creatinine ratio (RPC) (0.26 to 1.24) was evident at T0 and T1. A reduction in the means of RPC, uGGT, and uGGT/uCr was observed 10-15 days after OH. Despite the elevation of these markers, the concentration of creatinine (1.11 to 1.40 mg/dL), urea (40.07 to 67.16 mg/dL), and urinary specific gravity (1.027 to 1.028) only presented slight variation. In canine pyometra, complications secondary to acute renal injury may be present that may be mild and transient in most treated animals. As elevation in SDMA and RPC preceded changes in creatinine levels for the evaluation of glomerular filtration, tubular markers could assist in the early identification of renal damage in canine pyometra.(AU)

Catorze cadelas com diagnóstico de piometra foram estudadas em três tempos distintos, sendo no momento do diagnóstico (T0), 24 horas (T1) e 10 a 15 dias (T2) após a ovário-histerectomia (OH). O objetivo foi avaliar o uso de diferentes biomarcadores renais em cadelas com piometra e estimar suas precocidades diante do agravo. As médias em dimetilarginina simétrica (SDMA) (17,71 a 26,54µg/dL) e relação gama-glutamil transferase e creatinina urinária (uGGT/uCr) (1,06 a 2,62U/mg) variara, apresentando aumento em todos os momentos. Já a elevação do gama-glutamil transferase (uGGT) (56,61 a 128,12 U/L) e da razão proteína e creatinina urinárias (RPC) (0,26 a 1,24) foram evidenciadas nos dois primeiros tempos. Uma redução na média do RPC, uGGT e uGGT/uCr foi observada 10-15 dias após a implantação do tratamento (OH). Apesar da elevação desses marcadores, a concentração de creatinina (1,11 a 1,40mg/dL), ureia (40,07 a 67,16mg/dL) e densidade urinária (1,027 a 1,028) sofreram poucas variações. Em piometra canina, as complicações renais agudas secundárias podem estar presentes, ainda que leve e transitória nos animais tratados. Os marcadores tubulares foram considerados precoces na injúria renal aguda. Além disso, a SDMA e o RPC antecederam as alterações de creatinina em todos os tempos analisados.(AU)

Vincristine sulfate treatment influence on kidney function of female dogs with transmissible venereal tumor / Influência do tratamento com sulfato de vincristina na função renal de cadela com tumor transmissível venéreo

Chemotherapy agents have some undesirable and non-selective cytostatic effects. Considering that kidneys are vulnerable to drug-induced toxicity, this study evaluated renal injury caused by vincristine sulfate (VS) in 12 female dogs diagnosed with transmissible venereal tumor (TVT). The animals were treated with VS (0.025 mg/kg IV) every 7 days for 4 weeks. During treatment, the animals were subjected to clinical examination, blood count, serum measurement of symmetric dimethylarginine (SDMA), blood urea nitrogen (BUN), creatinine, alanine aminotransferase, and alkaline phosphatase. In addition, urinalysis and urinary gamma-glutamyl transferase (GGT) measurements were performed. All parameters were determined three times: before beginning the treatment (T0), after 14 days (T1), and after 28 days (T2). During the study period, there were no changes in serum urea or creatinine levels, urine specific gravity, or persistent proteinuria. Furthermore, urinary GGT measurement did not indicate tubular lesions, and consistent elevation of SDMA was found in only one patient above the reference range. The results showed that weekly therapy with VS as a single agent for 28 days does not induce renal injury in most cases.(AU)

Os agentes quimioterápicos possuem efeitos citostáticos indesejáveis e não seletivos. Considerando a vulnerabilidade renal à toxicidade induzida por drogas, este estudo avaliou a lesão renal causada pelo sulfato de vincristina (VS) em 12 cadelas com diagnóstico de tumor venéreo transmissível (TVT). Os animais foram tratados com VS (0,025 mg / kg IV) a cada sete dias, durante quatro semanas. No transcurso do tratamento, os animais foram submetidos a exame clínico, hemograma, dosagem sérica de dimetilarginina simétrica (SDMA), nitrogênio ureico sanguíneo (BUN), creatinina, alanina aminotransferase e fosfatase alcalina. Além disso, foram realizadas análises de urina e medições de gama-glutamil transferase (GGT) urinária. Todos os parâmetros foram mensurados em três tempos, antes do início do tratamento (T0), aos 14 dias (T1) e aos 28 dias (T2). Durante o período do estudo, não houve alterações nas concentrações de ureia ou creatinina séricas, na gravidade específica da urina ou proteinúria persistente. Além disso, a medição de GGT urinária não indicou lesões tubulares, e elevação consistente de SDMA foi encontrada em apenas um paciente acima do intervalo de referência. Os resultados mostraram que a terapia semanal com VS como agente único por 28 dias não induz lesão renal na maioria dos casos.(AU)