Background: Dysregulation in glomerular hemodynamics favors hyperfiltration in diabetic kidney disease (DKD). Although carnosine supplementation ameliorates features of DKD, its effect on glomerular vasoregulation is not known. We assessed the influence of carnosine and carnosinase-1 (CN1) on afferent glomerular arteriole vasodilation and its association with glomerular size, hypertrophy and nephrin expression in diabetic BTBRob/ob mice. Methods: Two cohorts of mice including appropriate controls were studied i.e., diabetic mice receiving oral carnosine supplementation (cohort 1) and human CN1 (hCN1) transgenic (TG) diabetic mice (cohort 2). Lumen area ratio (LAR) of the afferent arterioles and glomerular parameters were measured by conventional histology. Three-dimensional analysis using a tissue clearing strategy was also employed.Results: In both cohorts, LAR was significantly larger in diabetic BTBRob/ob vs non-diabetic BTBRwt/ob mice (0.41±0.05 vs 0.26±0.07; p<0.0001) and (0.42±0.06 vs 0.29±0.04; p<0.0001), and associated with glomerular size (cohort 1: r =0.55, p=0.001; cohort 2: r=0.89, p<0.0001). LAR was partially normalized by oral carnosine supplementation (0.34±0.05 vs 0.41±0.05; p=0.004), but did not differ between hCN1 TG and wild type (WT) BTBRob/ob mice. In hCN1 TG mice, serum CN1 concentrations correlated with LAR (r=0.90; p=0.006). Diabetic mice displayed decreased nephrin expression and increased glomerular hypertrophy. This was not significantly different in hCN! TG BTBRob/ob mice (p=0,06 and p=0,08, respectively).Conclusion: Carnosine and CN1 may affect intra-glomerular pressure in an opposing manner through regulation of afferent arteriolar tone. This study corroborates previous findings on the role of carnosine in the progression of DKD.

Chronic kidney disease (CKD) affects 10% of the population worldwide. It often leads to poor quality of life, especially among people suffering from end-stage CKD. Detection and treatment of the renal disorders at an early stage can help in postponing of end-stage disease as well as its treatment options, such as renal transplant and dialysis. The current routine measurement of glomerular filtration rate (GFR) includes methods that are expensive, cumbersome, time-consuming, inaccurate, often inconvenient and invasive for the patients. Non-invasive diagnostic techniques can help to overcome many of these drawbacks. This paper reviews the progress made in the field of transcutaneous GFR measurement as a way for a simpler, non-invasive, cheaper, and patient-friendly assessment of renal function. We have discussed the various markers designed in combination with different measurement devices for the measurement of GFR. Also, we have compared the different kinetic models used to study the marker's clearance from the plasma; which ultimately helps in calculating the GFR. Most of these techniques have been limited to pre-clinical studies until now, with promising results for their transition into clinical use in the near future.

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