Relationships of risk factors for pre-eclampsia with patterns of occurrence of isolated gestational proteinuria during normal term pregnancy

Background

Isolated gestational proteinuria may be part of the pre-eclampsia disease spectrum. Confirmation of its association with established pre-eclampsia risk factors and higher blood pressure in uncomplicated pregnancies would support this concept.

Methods

Data from 11,651 women from the Avon Longitudinal Study of Parents and Children who had a term live birth but did not have pre-existing hypertension or diabetes or develop gestational diabetes or preeclampsia were used. Proteinuria was assessed repeatedly (median 12 measurements per woman) by dipstick and latent class analysis was used to identify subgroups of the population with different patterns of proteinuria in pregnancy.

Results

Higher maternal pre-pregnancy body mass index (BMI), younger age, nulliparity and twin pregnancy were independently associated with increased odds of any proteinuria in pregnancy. Women who experienced proteinuria showed five patterns: proteinuria in early pregnancy only (≤20 weeks gestation), and onset at 21–28 weeks, 29–32 weeks, 33–36 weeks and ≥37 weeks gestation. There were higher odds of proteinuria onset after 33 weeks in obese women and after 37 weeks in nulliparous women compared with normal weight and multiparous women respectively. Smoking in pregnancy was weakly negatively associated with odds of proteinuria onset after 37 weeks. Twin pregnancies had higher odds of proteinuria onset from 29 weeks. In women with proteinuria onset after 33 weeks blood pressure was higher in early pregnancy and at the end of pregnancy.

Conclusions

Established pre-eclampsia risk factors were related to proteinuria occurrence in late gestation in healthy term pregnancies, supporting the hypothesis that isolated gestational proteinuria may represent an early manifestation of pre-eclampsia.     

Assessment of pregnancy in the late-gestation mare using digital infrared thermography

The objective of this study was to investigate use of digital infrared thermal imaging (DITI) to determine whether surface temperature gradient differences exist between pregnant and nonpregnant mares as a noncontact method to determine pregnancy status. On the day measurements were collected, each pregnant mare (n = 10; beginning at 292.4 ± 1.4 d of gestation) was paired with a nonpregnant mare (n = 17). Ambient temperature, DITI measurements (left and right flank, wither temperatures [i.e., animal surface control] and background temperature), and rectal temperatures were obtained every 7 d for 5 wk before parturition and for 3 wk after parturition. There were no differences (P > 0.10) in temperature of the left and right side within groups; therefore, data were pooled. Pregnant mares had a higher (P < 0.01) flank temperature than that of nonpregnant mares (36.0 ± 0.2 °C vs. 34.2 ± 0.2 °C, respectively). Moreover, the difference (2.4 °C) in flank temperatures between the pregnant and nonpregnant mares was greater when the ambient temperature was <19 °C. Flank and wither temperatures were positively correlated (R = 0.72; P < 0.01) and were positively correlated with ambient temperature (R = 0.48 and 0.64, respectively; P < 0.01). However, wither temperatures (skin control site) did not differ (P > 0.10) between pregnant and nonpregnant mares. In conclusion, late-gestation mares had higher flank temperatures than those of nonpregnant mares, regardless of environmental conditions, however discriminating abilities were greater when ambient temperature was lower. We inferred that DITI may have value in confirming mid- to late-gestation pregnancies in some species by noncontact means, as observed in the mare.     

Effects of ramipril and valsartan on proteinuria and renal function in patients with nondiabetic proteinuria

The renin-angiotensin system is involved in the progression of chronic renal disease of both diabetic and nondiabetic origin. The angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers have been demonstrated to reduce urinary protein excretion and attenuate the development of renal injury. This prospective, randomized, 12-month study assessed the effects of ramipril (N = 23) vs. valsartan (N = 22) vs. combination of ramipril and valsartan (N = 26) on proteinuria, renal function and metabolic profile in 71 patients with nondiabetic proteinuria with normal or slightly impaired renal function. Monotherapy with ramipril or valsartan and combination of these two drugs significantly reduced proteinuria, serum creatinine, cholesterol and triglycerides as well as systolic and diastolic arterial blood pressure. There was no significant difference among three study groups according to reduction of arterial blood pressure, serum cholesterol and triglycerides. At one year, a significant reduction in serum creatinine was recorded in all three study groups, whereas at 3 and 6 months a statistically significant reduction in serum creatinine was only observed in patients on combination therapy. In addition, at 3 months the reduction of proteinuria was significantly greater in patients on combination therapy than in those on either monotherapy. These results indicated the combination therapy with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers to be more efficacious than either monotherapy in reducing proteinuria and serum creatinine level in the first 3 (proteinuria and serum creatinine) or 6 (serum creatinine) months of treatment.     

Glomerular lysozyme binding in protein-overload proteinuria

Binding of the cationic molecule lysozyme to the glomerular basement membrane and to the glomerular epithelial cell coat was investigated in the glomerulus of normal female Wistar rats and in rats in which heavy proteinuria was induced by the daily administration of 1 g of bovine serum albumin. In normal rats the binding of lysozyme to the anionic groups in the glomerular basement membrane and the cell coat had no effect on the ultrastructure of the glomerular epithelial cell, in particular the foot processes were unchanged. In the proteinuric rats the lysozyme-binding to the glomerular basement membrane and the epithelial cell coat was completely lost in the damaged glomeruli. In the apparently normal glomeruli present in these proteinuric animals binding was similar to that seen in normal rats. These results suggest that in protein-overload proteinuria there is a loss of glomerular anion and hence a reduction in the glomerular charge barrier. This may account, at least in part, for the increased glomerular leak of negatively charged serum albumin in this experimental model of proteinuria.     

The significance of albuminuria; proteinuria

"Albuminuria" is an inadequate term; proteins other than albumin commonly appear in the urine. Proteinuria seems to depend upon failure of the tubules to reabsorb protein which has filtered through glomeruli. Its occurrence may be the result of abnormal plasma proteins, glomeruli or tubules. Proteinuria need not always be the result of a renal lesion, but may actually cause one. When proteinuria is discovered, it should arouse curiosity about the patient in general, not merely about his kidneys. Other clinical information is needed in order that treatment be directed appropriately.     

Assessment of fetal intracranial pathologies first demonstrated late in pregnancy: cell proliferation disorders

A considerable number of central nervous system pathologies remain undiagnosed during the first two trimesters of pregnancy. This group of disorders includes anomalies of brain proliferation, migration and cortical organization. Due to the fact that a detailed ultrasound examination of the fetal brain is usually not performed during the third trimester the diagnosis of these disorders is usually only made in families with a previously affected child or in many cases be mere chance. In this article we review the feasibility of prenatal diagnosis of disorders of brain proliferation: microcephaly, macrocephaly, hemimegalencephaly and neoplastic and non-neoplastic abnormal cell types. We discuss the differential diagnosis and offer a stepwise approach to the diagnosis of the more common disorders.     

Assessment of fetal number, and fetal and placental viability throughout pregnancy in cattle

Production of identical twin calves by embryo demisection requires a reliable system for continual monitoring of pregnancy. Both halves of bisected embryos were replaced nonsurgically into one uterine horn on Day 7 in 80 recipients. Monthly blood sampling began on Day 22 of pregnancy and transrectal echography took place between 50 and 80 days. Fifty-four recipients had elevated plasma progesterone concentrations on Day 22 (67% pregnancy rate). Of 21 pregnancies diagnosed as twins by echography, 15 live sets were born, 3 singles accompanied by a stillbirth, and 3 complete abortions. Twenty-five singleton pregnancies resulted in 23 live calves, 1 still-birth and 1 abortion. It was not possible to monitor echographically the remaining 8 pregnancies. At all stages of pregnancy studied, mean concentrations of bovine pregnancy-specific protein B (bPSPB) and estrone sulphate were higher (P<0.01) in twin (n = 17) than in single (n = 26) pregnancies, but the high individual variation obviated any predictive value for fetal number. Although bPSPB and estrone sulphate concentrations were positively correlated at most stages of normal pregnancies after Day 100, divergence was observed in the unsuccessful pregnancies between the concentrations of all 3 hormones, suggesting synthesis/release is under independent control. Measurement of bPSPB may be useful for prediction of fetal well-being, whereas estrone sulphate may reflect placental viability.     

Plasma fibronectin levels in patients with glomerular proteinuria

Plasma fibronectin concentration was measured by means of rocket immunoelectrophoresis in 20 cases of glomerular proteinuria of various origins, and correlated with urinary protein loss, serum albumin, cholesterol and plasma alpha 1 antitrypsin and alpha 2 macroglobulin. Plasma fibronectin was significantly increased in the patient's group as compared to the controls (1.91 +/- 0.659 U/ml, 1.01 +/- 0.193 U/ml respectively, p less than 0.001) and correlated with cholesterolaemia (r = 0.662, p less than 0.001). Increased plasma fibronectin may be an additional risk factor for thrombotic tendency in NS.