Kidney Damage Linked to GFR Changes During Pregnancy and Postpartum High Salt Diet

Population-based data demonstrated women that experience a preeclamptic event are at an increased risk for developing kidney disease after pregnancy relative to woman who have a normotensive pregnancy. Our group has demonstrated that Dahl salt-sensitive rats maintained on a low salt casein-based diet (SSC) develop pregnancy-specific increases in blood pressure and proteinuria, while Dahl SS rats maintained on a low salt wheat gluten-based diet (SSWG) are protected. Yet, it is unknown how postpartum renal function is impacted after pregnancy and whether dietary protein source can affect these outcomes. Therefore, we tested the hypothesis that following a single pregnancy SSC rats would exhibit a reduced glomerular filtration rate (GFR) and exacerbated kidney damage in response to a postpartum high salt (HS) diet. To test this hypothesis, we tracked GFR longitudinally via transdermal fluorescence detection (FITC-sinistrin) in SSC and SSWG rats at pre-pregnancy, late pregnancy, post-weaning, and following a 3-week postpartum high salt diet. In addition to tracking GFR, we measured urinary protein excretion throughout the study to assess markers of kidney damage. At baseline, the SSC exhibited a higher GFR relative to SSWG (2.6±0.2 vs 2.2±0.2 ml/min/100g BW, p >0.05, SSC vs SSWG, n=4/group) and a comparable urinary protein excretion rate (83±24 vs 81±21 mg/day, p >0.05, n=4/group). Despite the SSC exhibiting a slightly higher baseline GFR, both groups had comparable GFRs during late pregnancy (2.8±0.1 vs 2.9±0.3 ml/min/100g BW, p >0.05, SSC vs SSWG); however, the SSC had a smaller increase in GFR in response to pregnancy relative to the SSWG (D0.2±0.2vs 0.7±0.2 ml/min/100g BW, p> 0.05). GFRs remained comparable at the post-weaning time point; yet the SSC exhibited greater GFR following the recovery period before the high salt challenge (2.9±0.1 vs 2.2±0.2 ml/min/100g BW, p <0.05, SSC vs SSWG). At high salt day 21, GFRs were comparable between the groups (2.0±0.1 vs 2.2±0.2 ml/min/100g BW, p >0.05, SSC vs SSWG), but the delta change in the GFR was significantly greater in the SSC compared to the SSWG (D-0.9±0.1 vs -0.1±0.2, p <0.05). This reduction in GFR was accompanied with significant proteinuria in response to a high salt challenge (557±120 vs 209±19 mg/day, p <0.05, n=4/group). These results demonstrate that when GFR fails to increase during pregnancy it leads to lasting renal impairments that worsens the severity of a secondary insult such as a high salt diet.