The right renal vein enters directly into vena cava inferior, whereas the left renal vein crosses the maternal spine and runs between the aorta and the superior mesenteric artery before entering vena cava inferior. In late pregnancy, venous return from the left kidney may be obstructed between the spine/aorta and the growing uterus (Fig. 1).
Satyapal has classified anatomical variation of the drainage pattern from the kidneys and reported that there were extensive collaterals on the left side, and that the left renal vein had twice the length of the right vein.1 He suggested that abnormal venous flow may be associated to pathological conditions.2 A swine study has shown elevation of plasma serum aldosterone and plasma renin activity as well as urinary protein leakage as a consequence of increased left renal vein pressure.3 Increased venous pressure may cause microcirculatory congestion and impaired organ function also in humans.4
The size of the kidneys increases during pregnancy together with the increase of all aspects of the renal function.5Anatomic changes and adaptions are necessary for a successful pregnancy. It has been shown that the venous flow differs between the left and right kidney in uncomplicated third trimester pregnancies,6,7 and it has been suggested that venous congestion in the kidneys of pregnant women may be associated with the development of preeclampsia.8–11
In a previous study, we found lower venous blood flow in the left kidney compared with the right kidney in uncomplicated pregnancies, but no difference in arterial blood flow.6 The primary aim of the present study was to compare the parenchymal blood flow intensity (BFI) in the right and the left kidney. A secondary aim was to study possible associations between parenchymal BFI in the kidneys and maternal, labor and new-born characteristics.
From January to April 2018, we conducted a prospective cohort study at Trondheim University Hospital, Norway. We examined parenchymal BFI in the maternal kidneys in women with uncomplicated singleton pregnancies in the third trimester, between gestational week 30 and 34. The study was approved by the regional ethics committee with reference number REK 2017/1215, and all women gave informed written consent according to the Declaration of Helsinki.
In all, 51 women were examined with Doppler ultrasound. The transducer was placed in the flanks when the woman was sitting. A longitudinal view of both kidneys was obtained. The parenchymal BFI was assessed with dynamic color. Doppler tissue perfusion measurement using the Pixel Flux-software (http://www.chameleon-software.de/en/home.php). Data quantified the BFI during a complete heart cycle from a standardized color Doppler video clip (DICOM format). Flow velocities and perfused area were coded with colors, and the software calculated BFI by analyzing each pixel in the video clip with respect to its encoded flow velocity and area. The colors representing different velocities were displayed as a color scaling bar on the ultrasound screen. The color scaling bar was used to define the specific velocity value of each color hue. Velocities were calculated within the parenchyma distal to the outer margin of the medullary pyramids of one renal segment and divided into regions of interest as the proximal 50%, the proximal 25%, the distal 50% and the distal 25%. The cortical segment was defined as encompassing the cortical area between the watershed on the left and the watershed on the right side of an interlobar artery. BFI (cm/s) of a complete heart cycle was calculated from mean values (along the complete heart cycle) of the raw data as follows:
The unit of BFI is “cm/s.” However, BFI is fundamentally different from a pure velocity measurement since the ratio of perfused parenchyma to the entire parenchyma within the region of interest (ROI) is used to describe the vessel density of the ROI. Moreover, the mean values along a complete heart cycle are calculated by the software. Thus, the measurements are not flawed by data acquisition at an arbitrary time point during the heart cycle nor by an arbitrary region.
Videos with movement artifacts were excluded from perfusion quantification by a defined software algorithm. We also excluded cases where compatible areas were not recorded from both kidneys and cases where the periphery of the kidney was not included.
Three midwives with more than 10 years’ experience performing Doppler ultrasound were trained and did all examinations with a Voluson E8 machine (GE Medical Systems, Zipf, Austria), with a 3.5–7.5-MHz 3D curved multifrequency transabdominal transducer. A semi-automatic device (CAS 740. MAX NIBP) was used to measure maternal blood pressure immediately after the ultrasound examination, and pH in the umbilical artery was measured after birth with Bergman Diagnostika ABL 90 flex Radiometer.
The main outcome measure was parenchymal BFI in the renal cortex. Secondary outcomes were associations between parenchymal BFI in the entire cortex and maternal age, pre-pregnant body mass index, blood pressure, pH in the umbilical artery, Apgar score after 5 minutes and birthweight.
Parenchymal BFI in the left and right kidney were compared with Mann-Whitney U test. Associations between parenchymal BFI and maternal, labor and new-born characteristics were compared with linear regression. P < 0.05 was considered statistically significant. Data were analyzed with the statistical software package SPSS 25.0 (IBM, Armonk, NY, USA).
In all, 51 pregnant women were included in the study. The characteristics of the study population are presented in Table 1. Three women were excluded because the appropriate parenchymal region of one kidney was not included in the video clip, two because the region of interest was not comparable in the two kidneys, and 12 because of movement artefacts, leaving 34 women for analysis.
We found a significantly lower parenchymal BFI in the entire cortex of the left kidney compared with the right kidney; mean BFI 0.37 cm/s versus 0.69 cm/s, respectively (P = 0.04). An example of different parenchymal BFI in the two kidneys is illustrated in Figure 2. The BFI was significantly lower in the proximal 25% of the left renal cortex compared to the corresponding right side (P = 0.01), and in the proximal 50% cortex (P = 0.02), but the difference was not significantly different in the distal 25% (P = 0.06) or in the distal 50% (P = 0.20) of the renal cortex. Details are presented in Table 2 and Figure 3.
Correlations between renal BFI and maternal and new-born characteristics are presented in Table 3 and Table 4. We found a statistically significant negative correlation between BFI in the left kidney and both systolic blood pressure (r = −0.38, P = 0.03) and diastolic blood pressure (r = −0.36, P = 0.04) as illustrated in Figure 4. We did not observe any significant correlations between BFI and maternal or new-born characteristics in the right kidney.
Our main finding was lower BFI in the left kidney. We also observed that higher systolic and diastolic blood pressure were correlated with lower BFI in the entire cortex of the left kidney, but not with the BFI in the entire cortex of the right kidney. Another study from the same population has previously found that the volume flow in the left vein was lower than in the right vein, but showed no differences in volume flow in the renal arteries.6
The etiology of hypertension in pregnancy and preeclampsia is poorly understood, and several questions remain unanswered. Why is it mainly a human disease? Why is aspirin most effective during the night? Why is preeclampsia common in African women? We speculate that the uterus causes more pressure on the left renal vein than the right renal vein due to human upright posture. Upright posture causes lumbar lordosis, and this will press the spine from behind against the left renal vein, which is already compressed from the front by the pregnant uterus. If a woman is sleeping in a supine position, the uterus is pressed by gravitation against the left renal vein. Supine sleeping has been reported in 9.7% of women who experienced late-pregnancy stillbirth compared to 2.1% of women in a control group.12 Aspirin is used as a prophylactic drug in women with high risk of developing preeclampsia,13–15 but aspirin seems to be more effective on blood pressure when administrated at bedtime.16
Preeclampsia occurs spontaneously only in humans and higher apes,17 and the condition has huge impact on global maternal health.18 It is not explained, so far, why the prevalence of preeclampsia is higher in Africa. The prevalence of preeclampsia is around two percent worldwide,19 but up to 9% in Africa.20,21 and eclampsia is reported to occur in more than 1% of pregnancies in rural areas of Africa.22African women may have a differently shaped pelvis and more lumbar lordosis causing higher intra-abdominal pressure during pregnancy and more pressure on the left renal vein.23,24
Gyselaers et al. has described renal venous circulation and showed changes in the venous blood flow during pregnancy. They have suggested a possible association between abnormal venous flow and preeclampsia.7–11,25,26 Gyselaers and Thilaganathanhave recently described the interorgan interactions between the kidneys and the heart, and have introduced a theory that preeclampsia is a gestational manifestation of cardiorenal syndromes.27
The nutcracker syndrome occurs in nonpregnant women and men and results from an uplifting of the left renal vein by the anterior shift of the abdominal aorta due to a lumbar lordosis.28 The signs and symptoms are derived from outflow obstruction of the left renal vein, which causes renal vein hypertension, leading to hematuria, proteinuria, and abdominal pain.29,30 The left gonadal vein drains into the left renal vein (Fig. 1) and compression of the left renal vein may also result in varicocele and left testicular pain in men and the ovarian vein syndrome with left lower quadrant pain in women.31 The Pixel Flux method has been used for examining women with symptoms of left renal vein compression due to an exaggerated lumbar lordosis, and treatment with aspirin has shown improved circulation in the kidneys.32 We have hypothesized that uterus may further increase a preexisting lordotic compression, and this may influence development of late-onset preeclampsia. We realize that this small study cannot prove this hypothesis. Renal blood flow should be studied in women with preeclampsia, and the knowledge about differences in BFI in normal pregnancies is necessary for sample size calculations in new studies. We hope that the study will inspire other researchers. Parenchymal BFI in the kidneys should be studied in different populations, and more attention should be payed to complications associated with sleeping positions in late pregnancy. It will also be of interest to study ovarian vein congestion and to compare the excretion of protein from the right and left kidney in women with preeclampsia.
One strength of our study is that we measured renal parenchymal BFI through a complete heart cycle. The Pixel Flux method is a novel, objective method calculating flow intensities based on the color and area of each pixel of the image. However, the study has limitations. The study population was small and comprised only healthy women, but it was important to start our project investigating a normal population. Movement artifacts were difficult to avoid because of close relation to the pulsating aorta. However, the examiner of the video clips (Thomas Scholbach) did not perform ultrasound acquisitions, and he only included recordings of optimal quality.
We conclude that BFI in the left renal cortex was lower compared with the right renal cortex, and that BFI in the left renal cortex was negatively correlated with blood pressure.
The authors would like to thank Bente Simensen and Ingunn Aas for performing ultrasound examinations and Øystein Figenschou for making figure one and Kjell Åsmund Salvesen for editing the language.
Torbjørn Moe Eggebø had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Torbjørn Moe Eggebø and Thomas Scholbach. Acquisition of data: Eva Johanne Leknes Jensen. Analyzing ultrasound video clips with the Pixel Flux method: Thomas Scholbach. Analysis and interpretation of data: Torbjørn Moe Eggebø and Eva Johanne Leknes Jensen. Drafting of the manuscript: Eva Johanne Leknes Jensen, Ellen Aagaard Nohr, Thomas Scholbach, and Torbjørn Moe Eggebø.
Conflicts of Interest
Thomas Scholbach is the co-developer, scientific advisor, and shareholder of the Chameleon-Software GmbH.
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. Doty JM, Saggi BH, Sugerman HJ, et al. Effect of increased renal venous pressure on renal function. J Trauma 1999;47(6):1000–1003. doi:10.1097/00005373-199912000-00002.
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