Diabetic nephropathy (DN) is associated with albuminuria and loss of kidney function and is the leading cause of end-stage renal disease. Despite evidence of sexassociated differences in the progression of DN in human patients, male mice are predominantly being used in preclinical DN research and drug development. Here, we compared renal changes in male and female uninephrectomized (UNx) db/db C57BLKS mice using immunohistochemistry and RNA sequencing. Male and female UNx db/db mice showed similar progression of type 2 diabetes, as assessed by obesity, hyperglycemia, and HbA1c. Progression of DN was also similar between sexes as assessed by kidney and glomerular hypertrophy as well as urine albuminto-creatinine ratio being increased in UNx db/db compared with control mice. In contrast, kidney collagen III and glomerular collagen IV were increased only in female UNx db/db as compared with respective control mice but showed a similar tendency in male UNx db/db mice. Comparison of renal cortex transcriptomes by RNA sequencing revealed 66 genes differentially expressed (p < .01) in male versus female UNx db/db mice, of which 9 genes were located on the sex chromosomes. In conclusion, male and female UNx db/db mice developed similar hallmarks of DN pathology, suggesting no or weak sex differences in the functional and structural changes during DN progression. K E Y W O R D S albuminuria, animal model, diabetic nephropathy, mesangial expansion, uninephrectomy How to cite this article: Sembach FE, Fink LN, Johansen T, et al. Impact of sex on diabetic nephropathy and the renal transcriptome in UNx db/ db C57BLKS mice. Physiol Rep. 2019;7:e14333.

Overall, miRNAs are present in dog feces at measurable levels. Some miRNAs seem to be subject to a higher degree of degradation in samples stored at room temperature for 24 hours compared with samples frozen after collection at -20°C. The investigated miRNAs were stably expressed over time. This study provides the basis for further research on miRNA expression profiles as biomarkers for gastrointestinal cancer in dogs.

Cardiovascular and renal complications are the predominant causes of morbidity and mortality amongst patients with diabetes. Development of novel treatments have been hampered by the lack of available animal models recapitulating the human disease. We hypothesized that experimental diabetes in rats combined with a cardiac or renal stressor, would mimic diabetic cardiomyopathy and nephropathy, respectively. Diabetes was surgically induced in male Sprague Dawley rats by 90% pancreatectomy (Px). Isoprenaline (Iso, 1 mg/kg, sc., 10 days) was administered 5 weeks after Px with the aim of inducing cardiomyopathy, and cardiac function and remodeling was assessed by echocardiography 10 weeks after surgery. Left ventricular (LV) fibrosis was quantified by Picro Sirius Red and gene expression analysis. Nephropathy was induced by Px combined with uninephrectomy (Px-UNx). Kidney function was assessed by measurement of glomerular filtration rate (GFR) and urine albumin excretion, and kidney injury was evaluated by histopathology and gene expression analysis. Px resulted in stable hyperglycemia, hypoinsulinemia, decreased C-peptide, and increased glycated hemoglobin (HbA1c) compared with sham-operated controls. Moreover, Px increased heart and LV weights and dimensions and caused a shift from α-myosin heavy chain (MHC) to β-MHC gene expression. Isoprenaline treatment, but not Px, decreased ejection fraction and induced LV fibrosis. There was no apparent interaction between Px and Iso treatment. The superimposition of Px and UNx increased GFR, indicating hyperfiltration. Compared with sham-operated controls, Px-UNx induced albuminuria and increased urine markers of kidney injury, including neutrophil gelatinase-associated lipocalin (NGAL) and podocalyxin, concomitant with upregulated renal gene expression of NGAL and kidney injury molecule 1 (KIM-1). Whereas Px and isoprenaline separately produced clinical endpoints related to diabetic cardiomyopathy, the combination of the two did not accentuate disease development. Conversely, Px in combination with UNx resulted in several clinical hallmarks of diabetic nephropathy indicative of early disease development.

Lack of translation and irreproducibility challenge preclinical animal research. Insufficient reporting methodologies to safeguard study quality is part of the reason. This nationwide study investigates the reporting prevalence of these methodologies and scrutinizes the reported information’s level of detail. Publications were from two time periods to convey any reporting progress and had at least one author affiliated to a Danish University. We retrieved all relevant animal experimental studies using a predefined research protocol and a systematic search. A random sampling of 250 studies from 2009 and 2018 led to 500 publications in total. Reporting of measures known to impact study results estimates were assessed. Part I discloses a simplified two-level scoring “yes/no” to identify the presence of reporting. Part II demonstrates an additional three-level scoring to analyze the reported information’s level of detail. Overall reporting prevalence is low, although minor improvements are noted. Reporting of randomization increased from 24.0% in 2009 to 40.8% in 2018, blinded experiment conduct from 2.4% to 4.4%, blinded outcome assessment from 23.6% to 38.0%, and sample size calculation from 3.2% to 14.0%. Poor reporting of details is striking with reporting of the random allocation method to groups being only 1.2% in 2009 and 6.0% in 2018. Reporting of sample size calculation method was 2.4% in 2009 and 7.6% in 2018. Only conflict-of-interest statements reporting increased from 37.6% in 2009 to 90.4%. Measures safeguarding study quality are poorly reported in publications affiliated with Danish research institutions. Only a modest improvement was noted during the period 2009–2018, and the lack of details urgently prompts institutional strategies to accelerate this. We suggest thorough teaching in designing, conducting and reporting animal studies. Education in systematic review methodology should be implemented in this training and will increase motivation and behavior working towards quality improvements in science.