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Written by: Zachary Cerra & Anoushka Krishnan MD
AcademicCME (www.academiccme.com) is accrediting this educational activity for CE and CME for clinician learners. Please go to https://academiccme.com/kicr_blogposts/ to claim credit for participation.
Pregnancy is a time of change, sometimes drastic. In the mother, there are many changes that occur both physically and emotionally. While some are outwardly apparent, others can be more subtle. Have you ever wondered what happens to everyone’s favorite paired organ, the kidneys? The goal of this brief blog post is to discuss changes in kidney physiology during pregnancy, thereby enabling better care of our patients during this unique period.
Anatomic Changes
The kidneys undergo significant anatomical changes during pregnancy. It is expected that kidney volume increases roughly 30 percent, which corresponds with the increase in renal perfusion flow of roughly 30 percent. This volume increase is to be largely attributable to nephron hypertrophy, not hyperplasia. Another commonly observed structural change is hydronephrosis - mostly attributed to mechanical compression of the ureters. In fact, the right kidney is more often affected as a result of the angle in which the ovarian vessels enter the pelvis on the right making them more prone to compression as the fetus grows. This is not considered a pathological change and resolves spontaneously after delivery.
Hemodynamic Changes and Impact on GFR
In addition to the anatomic changes of pregnancy, the associated hemodynamic changes are just as impressive and require important homeostatic kidney response. Cardiac output increases by up to 30-40% and systemic blood pressure (BP) drops by 25-30% in response to a decrease in peripheral vascular resistance. This period of vasodilation is mainly attributed to release of the hormone relaxin and increased production of nitric oxide, resulting in decreased systemic BP despite an up-regulation of the renin- angiotensin- aldosterone system (RAAS). The increased RAAS activity is attributed not only to the traditional activation due to perceived reduction in kidney perfusion secondary to the systemic vasodilation, but also a variety of pregnancy-specific changes. These include extra-renal release of renin by the ovaries and maternal decidua and higher angiotensinogen synthesis in the liver in response to the increased circulating estrogen. Interestingly, the placenta itself has all of the components necessary to have an independent RAAS function, and there is some evidence that disbalance in the RAAS activation may contribute to pre-eclampsia. Aldosterone levels steadily rise from week eight up to the third trimester, resulting in 30-50% increase in plasma volume compared to non-pregnant women. There is also a net gain in sodium in the pregnant state, with retention of up to 350 mEq. However, the water retention due to increased circulating ADH results in a relatively greater increase in plasma volume resulting in decreased serum sodium measurement, resulting in a physiologic range of 130-135 mEq/L.
The large gain in blood volume also results in an impressive increase in the glomerular filtration rate (GFR) of nearly 40-50%, resulting in decreased serum creatinine levels. In fact, a “normal” creatinine by standard, non-pregnant norms may actually be abnormal in a pregnant patient. Twenty-four hour creatinine clearance remains the gold standard for estimating GFR in pregnant patients, as the Modification or Diet in Renal Disease (MDRD), and other commonly used equations underestimate GFR when greater than 45-60, and thus pregnant patients. When utilizing 24-hour creatinine clearance, measurements should be interpreted with caution as results can be affected by incomplete bladder emptying or mild hydronephrosis.
The exact mechanism leading to glomerular hyperfiltration is still under active investigation. It is believed that there are several contributory forces at play. The prevailing theory is the following: 1) there is a predominant increase in hydrostatic pressure due to the increase in plasma volume, 2) there is a slight increase in the permeability factor of nephrons driven by both hypertrophy and increased permeability, and 3) a decrease in serum oncotic pressure due to a decrease in serum osmolality. These mechanisms play varying roles in a net hyperfiltration effect.
Nephron permeability also changes with pregnancy, thereby resulting in proteinuria measurements as high as 300 mg per day (correlating to 2+ proteinuria on urine dipstick), which is still considered normal in pregnancy. Thus, proteinuria seen on a dipstick should always be quantified. Higher levels of proteinuria (>300mg/d) are considered abnormal. If present prior to 20 weeks of gestation, proteinuria can reflect the presence of pre-existing/primary kidney disease but if present after 20 weeks of gestation, preeclampsia should be considered.
Tubular Function Changes
Pregnancy not only affects kidney filtration and hemodynamics, but there are also direct impacts on renal tubular function. The physiological changes in renal tubular function include glycosuria, decreased reabsorption of uric acid, amino acids and ꞵ-2-microglobulin resulting in increased excretion of these substances. Typically, glycosuria is seen only in states of hyperglycemia where the filtered load exceeds the maximal tubular reabsorption; however, in the pregnant state, there appears to be a decreased capacity for reabsorption, and thus pregnant patients may exhibit glycosuria at normoglycemic levels. It has also been observed that serum uric acid levels fall, presumably due to increased excretion of uric acid. This process is attributed to a combination of hyperfiltration and decreased proximal tubular reabsorption. The effects on glucose and uric acid reabsorption vary between pregnant patients and may be present or absent in the same patient at different stages of pregnancy. The exact mechanism by which these changes in tubular reabsorption occur are still under active investigation.
Conclusion
In conclusion, pregnancy is associated with many changes that affect the kidneys. Most notable include kidney hypertrophy, mild hydronephrosis, increased blood volume, GFR increase of 40-50%, decrease in blood pressure (due to reduced peripheral vascular resistance), and alterations in electrolytes like hyponatremia and mid-trimester dip in serum creatinine (check if mid trimester, can also occur in first trimester). By understanding the anticipated physiologic changes in pregnancy, we can better serve this population by staying vigilant in identifying pathophysiologic processes in pregnancy warranting further investigation.
AcademicCME (www.academiccme.com) is accrediting this educational activity for CE and CME for clinician learners. Please go to https://academiccme.com/kicr_blogposts/ to claim credit for participation.