Pipeline F - Kidney funtion
This pipeline can be applied to evaluate renal function in living mice in cases of alterations in biomarkers of renal function found in the primary phenotyping screen or previously known effects on kidneys in the model investigated. This is of high relevance for one of the objectives proposed by the GMC, which relates to the study of metabolic derangements underlying the clinical manifestations of diabetes and its late onset complications such as diabetic nephropathy.
In this pipeline blood samples are withdrawn to determine plasma concentrations of relevant parameters such as electrolytes, minerals, total protein and albumin, creatinine, urea, uric acid, glucose etc. few days before urine collection. Thereafter, 24- or 48-hour urine samples are collected using metabolic cages for single housed mice. In case of decreased urine concentration, water deprivation can be applied to test urine concentration ability. Water and food uptake as well as urine and feces production can be quantified. In addition, from the clinical chemical analyses of plasma and urine samples, creatinine clearance, 24hour excretion and fractional excretion rates of measured urinary components can be calculated (Fuchs et al., 2011).
As part of the kidney function hypothesis-driven pipeline, the pathology screen determines absolute and normalized kidney weights and performs a morphological evaluation of the renal system supported by standard and special tissue stainings and immunohistochemistry in agreement with the guidelines and standards set by the Animals Models of Diabetic Complications Consortium (AMDCC) (Alpers & Hudkins, 2011).
Fuchs, H et al. (2011) Mouse phenotyping. Methods 53, 120-135Alpers, CE and Hudkins, KL (2011) Mouse Models of Diabetic Nephropathy. Curr Opin Nephrol Hypertens 20, 278–284