Development of the Diabetic Kidney Disease Mouse Model Culturing Embryos in α-Minimum Essential Medium In Vitro, and Feeding Barley Diet Attenuated the Pathology.

Diabetic kidney disease (DKD) is a critical complication associated with diabetes; however, there are only a few animal models that can be used to explore its pathogenesis. In the present study, we established a mouse model of DKD using a technique based on the Developmental Origins of Health and Disease theory, i.e., by manipulating the embryonic environment, and investigated whether a dietary intervention could ameliorate the model's pathology. Two-cell embryos were cultured in vitro in α-minimum essential medium (MEM; MEM mice) or in standard potassium simplex-optimized medium (KSOM) as controls (KSOM mice) for 48 h, and the embryos were reintroduced into the mothers. The MEM and KSOM mice born were fed a high-fat, high-sugar diet for 58 days after they were 8 weeks old. Subsequently, half of the MEM mice and all KSOM mice were fed a diet containing rice powder (control diet), and the remaining MEM mice were fed a diet containing barley powder (barley diet) for 10 weeks. Glomerulosclerosis and pancreatic exhaustion were observed in MEM mice, but not in control KSOM mice. Renal arteriolar changes, including intimal thickening and increase in the rate of hyalinosis, were more pronounced in MEM mice fed a control diet than in KSOM mice. Immunostaining showed the higher expression of transforming growth factor beta (TGFB) in the proximal/distal renal tubules of MEM mice fed a control diet than in those of KSOM mice. Pathologies, such as glomerulosclerosis, renal arteriolar changes, and higher TGFB expression, were ameliorated by barley diet intake in MEM mice. These findings suggested that the MEM mouse is an effective DKD animal model that shows glomerulosclerosis and renal arteriolar changes, and barley intake can improve these pathologies in MEM mice.

Incidence and predictive factors of Balkan endemic nephropathy: a longitudinal study.

Balkan endemic nephropathy (BEN) is a chronic kidney disease that progresses slowly. There are no known clinical markers to identify an early disease development. We evaluated the relationship between parental history of BEN and clinical markers as predictors of new occurrences of BEN. A 5-year prospective study in the offsprings of BEN and control patients was conducted in Vratza, Bulgaria, between 2003 and 2009 using markers in years one and three to predict new cases of BEN in the year five. We defined incident cases of BEN based on parental history, reduced kidney size and reduced kidney function, distinguishing probable and definite BEN, both combined as total incidence. The data were analyzed by Cox regression models using age as time scale and controlling for gender. We estimated hazard ratios and their 95% confidence intervals. The incidence of BEN was 17.4%. Paternal history was strongly associated with all three incidence groups (hazards ratio: 27-68, P <0.05). A reduction of kidney size of 1 mm resulted in a 5% increased hazard. However, taking parental history of BEN into account, these associations lost their significance. No kidney function measures were associated with new onset of BEN. A parental history of BEN is more important than clinical markers predicting the incidence of BEN. Without this information, kidney length forecasts probable BEN and the total incidence, while none of any clinical markers was related to definite BEN.

Birth weight--a risk factor for progression in diabetic nephropathy?

OBJECTIVES: Intrauterine growth retardation, as seen in individuals with low weight at birth, may give rise to a reduction in nephron number. Oligonephropathy has been linked to hypertension and renal disease in adult life. We tested the concept that low weight at birth acts as a risk factor for progression of diabetic nephropathy. DESIGN AND SUBJECTS: We performed an observational follow-up study of 161 (97 men) type 1 diabetic patients with diabetic nephropathy [mean age (SD): 35 (11) years, mean duration of diabetes: 22 (8) years]. All patients had been followed for at least 3 years [median (range): 8 (3-20)] with at least three measurements [9 (3-31)] of glomerular filtration rate (GFR) (51Cr-EDTA). Information about birth size was obtained from midwife registrations. SETTINGS: Steno Diabetes Center, a tertiary referral centre. MAIN OUTCOME MEASURES: Loss of kidney function according to birth weight and weight/length ratio at birth. RESULTS: There was no correlation in univariate analysis between birth weight or weight/length ratio and rate of decline in GFR, neither in men nor in women. Furthermore, the 27 patients with birth weights below the 20th centile had a rate of decline in GFR [median (range)] similar to the 134 patients above: 2.6 (-4.7; 9.6) vs. 3.4 (-2.3; 19.3) mL min(-1) year(-1), respectively (NS). A multiple regression analysis revealed that albuminuria, arterial blood pressure, and haemoglobin A1C during follow-up showed a significant correlation with the decline in GFR [R2 (adjusted) = 0.34], whereas birth weight and birth weight/length ratio did not. CONCLUSIONS: Our study does not suggest that weight at birth is associated with progression of established diabetic nephropathy in type 1 diabetic patients, whilst several other potential modifiable risk factors were identified.

Is low birth weight a risk factor for the development of diabetic nephropathy in patients with type 1 diabetes? A population-based case-control study.

OBJECTIVES: To investigate if low birth weight as a consequence of intrauterine malnutrition is a risk factor for the later development of diabetic nephropathy. DESIGN AND SUBJECTS: In a case-control set-up a group of type 1 diabetic subjects with diabetic nephropathy (n = 51) and a matched control group with normal kidney function (n = 51) were compared. Diabetic nephropathy and normal kidney function were defined as urinary albumin excretion rate above 200 microg min-1 and below 20 microg min-1, respectively. The birth weights were all obtained from the midwives' original records. SETTING: The patients were identified from a population-based study of chronic diabetic complications in the Funen County, Denmark. MAIN OUTCOMES: Birth weights according to the presence of diabetic nephropathy. RESULTS: The median (10-90 percentile) birth weights were 3,600 g (2,960-4,274) in the group with diabetic nephropathy and 3,600 g (2,880-4,220) in the group without nephropathy, P = 0.52. In the lower quartile of birth weights the median (10-90 percentile) birth weights were 3,000 g (2,780-3,200) in the group with nephropathy versus 2,850 g (2,250-3,175) in the group without nephropathy, P = 0.07. In the upper quartile the median (10-90 percentile) birth weights were 4,225 g (4,000-4,741) in the nephropathy group and 4,000 g in the group without nephropathy, P = 0.13. We found no significant correlation between birth weights and log urinary albumin excretion rate (r = 0.148, P = 0.14) and no difference in the number of patients with nephropathy in the lower versus upper quartiles of birth weights. CONCLUSION: We found no evidence of low birth weight as a risk factor for the development of diabetic nephropathy.