Impact of Pregnancy on Underlying Renal Disease

Abstract

Normal pregnancy involves marked renal vasodilation and large increases in glomerular filtration rate (GFR). Studies in rats reveal that the gestational renal vasodilation is achieved by parallel reductions in tone in afferent and efferent arterioles so GFR rises without a change in glomerular blood pressure. There is some evidence from animal studies that increased renal generation of nitric oxide (NO) may be involved. Although chronic renal vasodilation has been implicated in causing progression of renal disease in nonpregnant states by glomerular hypertension, there are no longterm deleterious effects of pregnancies on the kidney when maternal renal function is normal because glomerular blood pressure remains normal. When maternal renal function is compromised before conception, there are no long-term adverse effects on renal function in most types of renal disease, providing that the GFR is well maintained before conception. When serum creatinine exceeds ~ 1.4 mg/dL, pregnancy may accelerate the renal disease increases and when serum creatinine >2 mg/dL, the chances are greater than 1 in 3 that pregnancy will hasten the progression of the renal disease. The available animal studies suggest that glomerular hypertension does not occur despite diverse injuries. Thus, the mechanisms of the adverse interaction between pregnancy and underlying renal disease remain unknown. Index WordsGlomerular filtration rate; renal vasodilation; animal models; primary glomerular disease; diabetes There are profound hemodynamic changes in normal pregnancy including increases in plasma volume, red blood cell volume, and hence blood volume. Both stroke volume and heart rate increase leading to ~40% elevations in cardiac output, despite which, blood pressure (BP) falls because of large reductions in total peripheral vascular resistance (TPVR). [1][2][3] In addition to peripheral vasodilation, a vascular refractoriness to a variety of administered vasoconstrictors including angiotensin II develops quite early. [2][3][4] Striking changes also occur in kidney function, with an early increase in glomerular filtration rate (GFR), which is first detectable within 3 to 4 weeks after conception (Fig 1). 5 GFR continues to rise to a maximum of 40% to 50% above nonpregnant values by the end of the first trimester, and this increase is maintained throughout most of the pregnancy, although a fall in GFR occurs in the few weeks before delivery. 6 An optimal increase in GFR is a good prognosticator for a successful pregnancy outcome. As shown in Figure 1, in a serial study of normal pregnant women, 2 women who failed to show the early rise in GFR subsequently underwent early spontaneous abortion. 5 The rat is an excellent animal model for study because it exhibits systemic and renal hemodynamic changes during normal pregnancy that are similar to humans and the total gestation period in rats is only 22 days (Fig 2) volume expansion (which can reach 100% above the nonpregnant rat value) followed by a fall in blood pressure (although this is...

Changes in renal hemodynamics and structure in the aging kidney; sexual dimorphism and the nitric oxide system

“…There is less information about the impact of progesterone, which has been reported to enhance some and oppose other estrogen-mediated effects (Orshal and Khalil, 2004). However, multiple pregnancies in women and rats with normal renal function have no adverse impact on aging changes in kidney function and structure (Baylis, 2003), suggesting no harmful effect on the kidney of periodic elevations in progesterone levels.…”

Chronic Renal Disease in Pregnancy

“…25 Moreover, women with a serum creatinine level greater than 2.0 mg/dL should be counseled that they have a one-in-three chance of progressing to end-stage renal disease within 1 year postpartum. 6,26 Pregnant women requiring dialysis are at an even higher risk for complications and adverse pregnancy outcomes.…”

Pregnancy in Women with Renal Disease. Part I: General Principles

“…If any damaging effects of pregnancy on residual renal function occur, they are most likely secondary to nonhemodynamic mechanisms. 4 The increased RPF in pregnancy is the consequence of profound reductions in renal afferent and efferent arteriolar resistances. The ovarian hormone relaxin has been recently implicated as the mediator of renal vasodilatation in pregnancy.…”

“…Severe functional impairment (serum creatinine > 2. 4 to 2.8 mg/dL) There is a relationship between the degree of renal impairment and physiological adaptation to pregnancy. With mild renal impairment, there is normal intravascular volume expansion as well as expected increments in RPF and GFR, although somewhat less than in normal pregnancy.…”