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Purpose After observing variation in the expression of the housekeeping gene B2M in cells of the urinary sediment during a study of candidate genes potentially involved in diabetic kidney disease (DKD), we hypothesized that B2M mRNA expression in the urinary sediment could reflect the presence of DKD. Methods qPCR was used to quantify B2M mRNA expression in cells of the urinary sediment of 51 type 1 diabetes (T1D) patients (61% women, 33.5 [27.0–39.7] years old, with diabetes duration of 21.0 [15.0–28.0] years and HbA1c of 8.2% [7.3–8.9]; median [interquartile interval]) sorted according to the diabetic nephropathy (DN) stages; 8 focal segmental glomerulosclerosis (FSGS) patients and 10 healthy controls. B2M mRNA expression was also evaluated in human embryonic kidney epithelium-like (HEK-293) cells exposed to 25 mM glucose and to albumin in order to mimic, respectively, a diabetic and a proteinuric milieu. Results No differences were found in B2M mRNA expression among healthy controls, FSGS and T1D patients. Nonetheless B2M mRNA expression was higher in the group composed by T1D patients with incipient or overt DN combined with FSGS patients versus T1D patients without DN combined with healthy controls ( P = 0.0007). B2M mRNA expression was higher in T1D patients with incipient or overt DN versus without DN ( P = 0.03). B2M mRNA expression positively correlated with albuminuria in the overall T1D population (r = 0.43; P = 0.01) and negatively correlated with estimated glomerular filtration rate in male T1D patients (r = − 0.57; P = 0.01). Increased B2M expression was observed in HEK-293 cells exposed to 25 mM glucose and to albumin. Conclusions Β 2M mRNA expression in cells of the urinary sediment is higher in T1D patients with DKD and in patients with FSGS in comparison to healthy subjects, maybe reflecting a tubulointerstitial injury promoted by albumin. Given the proinflammatory nature of B2M, we suggest that this protein contributes to diabetic (and possibly, to non-diabetic) tubulopathy. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effect of experimental hyperleptinemia for 7 days and the participation of the Renin-Angiotensin II System (RAS) on renal function and morphology.Methods: 40-days male Wistar rats were divided into 4 groups (n = 5 - 6 per group): sham (Sh), Leptin (Lep; s.c. infusion 0.5mg/kg/day, osmotic pump, Alzet), Losartan (Los; s.c. 10 mg/kg/day), Leptin plus Losartan (LL). Systolic blood pressure (SBP) was measured by tail-cuff method. On 8th day, rats were anesthetized and prepared to renal clearance experiments. Renal plasmatic flow (RPF) and glomerular filtration rate (GFR) were determined by p-Aminohippuric acid sodium and inulin clearance. Urinary NH4+, pH, Na+, K+ and osmolality were analyzed. Renal tissue was submitted to histological studies.Results: 7-days Leptin treatment increased SBP (Sh: 105,8 ± 0,7 vs Lep: 118,0 ± 1,5 mmHg; ∗p<0.0001) and LL group reversed this parameter (LL: 103,4 ± 0,7 mmHg; ∗p<0.0001). Our preliminary results showed that Leptin and/or Losartan treatment does not affect renal hemodynamic (RPF - Sh: 20,48 ± 0,77 vs Lep: 15,79 ± 1,02 vs Los: 17,96 ± 2,21 vs LL: 18,99 ± 1,54 ml/min/kg and GFR - Sh: 7,94 ± 0,46 vs Lep: 9,19 ± 0,59 vs Los: 7,46 ± 0,60 vs LL: 6,97 ± 0,52 ml/min/kg). However, filtration fraction increased significantly in Lep group (Sh: 40,40 ± 1,72 vs Lep: 59,79 ± 2,46 %∗; ∗p < 0.0001) and was corrected by Losartan (LL 34,42 ± 3,06 % #; # p< 0.0001). Urinary flux increased in Lep rats and was also corrected by Losartan (Sh: 0,18 ± 0,01 vs Lep: 0,25 ± 0,02; ∗p<0.001 vs LL: 0,18 ± 0,008#; #p< 0.0001 ml/min/kg). Na+ excretion, which had an 337% increase in Lep group, was normalized in LL. Urinary excretion of NH4+ and K+ and urinary osmolality was not different between the studied groups. All parameters of Los group were not statistically different from Sh rats. Lep rats showed an increase in total glomerular area, which was also corrected in LL rats (Sh: 6708 ± 62 vs Lep: 7796 ± 130 vs Los: 6779 ± 23 vs LL 6822 ± 20 μm2).Discussion: Lep rats showed higher SBP, but not hypertension. Although there were no significant changes in renal hemodynamic, Leptin treatment caused glomerular hypertrophy. As many parameters were corrected by co-treatment with Losartan, it seems that RAS has a critical role in hyperleptinemic induced renal changes. [ABSTRACT FROM AUTHOR]