Why does gfr increase during pregnancy

However, as noted above, the results were statistically homogeneous across groups with different preeclampsia status. In Table 3 we have summarized the available data on the relationship of birth weight with estimated maternal GFR.

The data are from two previous studies [10] , [12] and the present analyses. All three studies indicate a relationship, with partial correlation coefficients for the two previous studies of 0. For the CG-based estimate, e. The absolute values and difference in GFR between formulas were in accordance with previous studies in pregnant women [14]. When summarizing all available data on the issue, including two previous studies [10] , [12] all three studies indicate a relationship, with partial correlation coefficients of 0.

When stratifying on preeclampsia, we found statistically significant results only for women with preeclampsia, which confirmed that including women with preeclampsia in the total cohort increased the study power, because it increased the proportion of small-for-gestational-age SGA newborns in the analysis [21]. Although the estimates of the relationship between birth weight and GFR from the present two earlier studies [10] , [12] appeared different, they were not only qualitatively in agreement, but they were also statistically homogeneous.

Nonetheless, the coefficients for the birth weight-GFR relation in the two previous studies by Gibson [10] and Dunlop [12] seemed quite different from one another despite that inulin clearance the gold standard method of estimating GFR was used.

Both studies were performed on limited number of patient 20 and 25, respectively. The study by Gibson [10] , however, had three SGA infants and this may account for why that study had sufficient power to detect a birth weight-GFR relationship. The subjects in the Dunlop study [12] had a narrow range of birth weights, and none of the infants were SGA, and that may explain why the standard error is relatively large in that analysis.

Even though eGFR is not as precise or accurate as inulin clearance, the much larger sample size and inclusion of many more SGA newborns in the present study not only strengthened the evidence that an association exists, but resulted in a direct, quantitative estimate of the size of the association, which will be of use in epidemiologic and pharmacokinetic studies.

To our knowledge this is the first study to estimate the relationship between fetal size and GFR in direct, quantitative terms. While the relationship between birth weight and GFR is statistically significant, the magnitude of the relationship, as reflected intuitively by the partial correlation coefficient of 0. Nonetheless, this modest relationship may result in significant confounding in studies of birth weight in relation to PFAS concentrations. Except for the adjustment for preeclampsia, this is the model of birth weight and PFOA in Whitworth et al.

Plasma creatinine was not measured in the Whitworth et al. The estimated association between GFR and infant birth weight will tend to be influenced by random errors in measurement of plasma creatinine and more accurate assessments of the relationship would need to be based on GFR gold standard measurements rather than eGFR. Others have found an intraclass correlation coefficient of 0.

New York: Oxford University Press. Pregnancy induces marked changes in renal function characterized by hyperfiltration, accompanied by systemic vasodilatation and plasma volume expansion that is fully established in mid-pregnancy [23] , [24]. Several methods are available to measure GFR, however, no consensus exists on what method is the most suitable in pregnancy [14]. The gold standard method of estimating GFR is inulin clearance, a costly and time consuming examination, unsuitable for large scale settings, like our study and in clinical settings.

The CKD-EPI formula showed no significant association with birth weight in the total cohort, but only when the women with preeclampsia were analyzed alone. This formula is an even poorer predictor of GFR in some groups [25] , especially pregnant woman [26] , which may explain the divergence in results. The major strength of our data was the large sample of women who had their GFR estimated compared to the previous studies [9] , [10] , and the relatively large proportion of newborns who were SGA.

Despite the strengths, our data have some limitations. Data on maternal weight were obtained from questionnaires and were self-reported. In general, self-reported weight is fairly accurate and precise, and that might be even more true during pregnancy [27] — [29]. Shipment of blood samples for a day at ambient temperature may have affected creatinine values in this study. The delayed separation of whole blood and ambient temperature may have increased levels of plasma creatinine [30].

Thus, our estimates of GFR may have been too low and more imprecise than usual; however, the effect on our estimate of the birth weight-GFR relationship would be to bias it towards the null.

The most important weakness of the present study, however, was that the estimate of GFR used was imprecise compared with direct measures of GFR, based on clearance. This number could be decreased by enriching the sample with SGA infants [21] , which could perhaps be done using mid-pregnancy ultrasound. These data support a modest, positive association between GFR during pregnancy and infant birth weight, and indicate that GFR may confound selected epidemiologic associations.

The quantitative estimate of the relationship presented, although provisional until better estimates become available, will also inform pharmacokinetic studies of the extent of such confounding.

Kristian Heldal and Carmen Williams provided insightful comments on an earlier draft of this manuscript and are acknowledged. We are grateful to all the participating families in Norway who take part in this on-going cohort study. Wrote the paper: NHM. Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field. Abstract Background The relationship of maternal glomerular filtration rate GFR in pregnancy to fetal size needs to be better characterized as it impacts an ongoing debate about confounding effect of maternal GFR in investigations of important environmental contaminants.

Materials and Methods A sub-cohort of selected women women with and women without preeclampsia in the Norwegian Mother and Child Cohort MoBa , recruited during — were analyzed. Conclusion These data support an association between GFR during pregnancy and infant birth weight, and indicate that GFR may confound selected epidemiologic associations. Introduction The relationship of glomerular filtration rate GFR in pregnancy to fetal size needs to be better characterized because the size of the association impacts an important ongoing debate in environmental health.

Lab analyses of plasma creatinine and GFR estimation Maternal non-fasting blood samples were collected at enrollment in the MoBa cohort at the time of the second trimester ultrasound scan. Results The characteristics of the included women are outlined in Table 1. The stress of increased renal blood flow and inability of the glomerulus to regulate intraglomerular pressure, which normally remains unaltered during pregnancy, may exacerbate renal damage in pre-existing disease.

Managing dialysis and renal transplant patients. CKD is generally characterised by menstrual disturbances and infertility, and is reversed by transplantation but not by dialysis. When pregnancy does occur, it needs to be co-managed by a nephrologist and an obstetrician as significant changes in management are required to improve maternal and neonatal outcomes. Transplant patients should also be co-managed as immunosuppressive drugs may need to be altered and their plasma levels will need to be carefully monitored.

Pregnant women who have a transplanted kidney with renal dysfunction should be considered in the same way as other patients with CKD. Pregnancy-induced acute kidney injury.

Acute kidney injury AKI in pregnancy may be caused by any of the disorders leading to renal failure in the general population, e. There are, however, pregnancy-related complications characteristic of each trimester that can result in renal failure. In the second and third trimesters, pregnancy-specific conditions, e. At delivery, placental abruption can be associated with severe ATN and bilateral cortical necrosis. The management of AKI is similar to that in a non-pregnant patient, with fluid management being especially important, particularly in the context of pre-eclampsia, as the vascular endothelium is very leaky.

Potential nephrotoxins such as the non-steroidal anti-inflammatory drugs NSAIDs and aminoglycosides should be used with caution throughout the pregnancy.

Managing the complicated patient. Diabetic nephropathy is frequently encountered during pregnancy. Pre-pregnancy counselling is important, as obstetric and renal outcomes are determined by the degree of peripartum CKD. There is no increased risk of overt nephrophathy or end-stage renal disease in women with normal renal function at conception. Women with lupus nephritis should be advised to conceive after a 6-month period of quiescent disease. There is also an increased risk of pre-eclampsia.

Extra-renal disease flare-ups are more common in the second and third trimesters, and postpartum flare-ups have been described. Flare-ups can be managed with corticosteroids. Maintenance therapy with azathioprine and hydroxychloroquine is considered safe. Tacrolimus and cyclosporin can be used in pregnancy with therapeutic drug level monitoring. Differentiating between a flare-up of lupus nephritis and pre-eclampsia may be challenging. Calcineurin inhibitors, glucocorticosteroids and azathioprine are the mainstay of safe immunosuppressive therapy in pregnant transplant recipients and lupus patients.

Mycophenolate mofetil has been reported to cause developmental toxicity, malformations, and intrauterine death in animals, with growing evidence confirming its teratogenic effects in humans.

The drug should be discontinued 6 weeks before conception. Because there are substantial physiological changes that occur in a normal pregnancy, it is necessary to understand these in order to determine whether the kidney developed disease during pregnancy.

Both pre-existing hypertension and renal disease increase the risk of adverse pregnancy outcomes and increase the risk of pre-eclampsia, which predisposes to preterm delivery.

Pregnancy in a patient with CKD may cause progression of renal failure, and in the SA setting this is complicated by restricted access to dialysis in the state sector. To ensure the best outcome for mother and child, pre-pregnancy counselling is essential.

Attention must be paid to the numerous teratogenic drugs that are commonly used to treat hypertension and the immunosuppression necessary to treat renal transplant recipients and those with glomerulonephritis e. Patients with renal disease and hypertension are at high risk of complications and regular antenatal assessments are required that should involve a multidisciplinary team to monitor BP, proteinuria, diabetic control and fetal wellbeing. Hydronephrosis during pregnancy: A literature survey.

Levey AS. Use of glomerular filtration rate measurements to assess the progression of renal disease. Semin Nephrol ; Assessment of glomerular filtration rate during pregnancy using the MDRD formula. Br J Obstet Gynaecol ; Estimation of glomerular filtration rate in preeclamptic patients. Am J Perinatal ; Am J Kidney Dis ; American College of Obstetricians and Gynecologists. Diagnosis and management of preeclampsia and eclampsia. Int J Gynaecol Obstet ; Use of protein: Creatinine ratio measurements on random urine samples for prediction of significant proteinuria.

A systematic review. Clin Chem ; Expanded Executive Summary. Pretoria: Department of Health, Fortnightly review: Management of hypertension in pregnancy. Br Med J ; Sibai BM. Treatment of hypertension in pregnant women. N Engl J Med ; Adverse perinatal outcomes and risk factors for preeclampsia in women with chronic hypertension: A prospective study. Hypertension ; Despite these problems, creatinine clearance still remains the most useful measure of GFR in clinical practice.

Urinalysis is essentially unchanged during pregnancy. However, many variables can affect the results. Normal kidneys should be able to concentrate urine to a specific gravity of 1. In pregnancy, posture affects urine concentration and specific gravity.

Urine tends to be more dilute after a left lateral position is maintained compared with an upright position. Dipsticks exposed to air will give false-positive results for glucose and false-negative results for blood. Proteinuria diagnosed on dipstick should be confirmed with a hour urine. The method of collection is very important when collecting a urine specimen.

It is difficult for the woman to obtain a satisfactory clean voided specimen by herself, especially when she is far along in pregnancy. In addition, the specimen must be collected before the pelvic examination; it may be collected by the examiner while the patient is in the dorsal lithotomy position.

The diagnosis of renal disease in pregnancy should begin by taking a careful history and performing a thorough physical examination. Particular attention should be directed toward any history of renal disorders, proteinuria, hypertension, collagen vascular diseases, or glycosuria affecting either the patient or close relatives.

Physical examination includes inspection of the optic fundi. Signs of uremia are usually a late feature in the natural progression of renal disease and indicate significant dysfunction. Laboratory investigation begins with urinalysis of protein, glucose, ketones, specific gravity, and sediment.

Glucosuria is usually detected with a glucose oxidase-impregnated dipstick. In pregnancy, the most common reasons for persistent glucose in the urine are physiologic glucosuria of pregnancy and diabetes. However, the possibility of primary renal disease with renal glucosuria should be considered.

Conventional screening for proteinuria uses a dipstick that is sensitive to albumin. Five percent of healthy adults exhibit postural proteinuria, a benign condition; this can be ruled out by comparing protein levels in the first voided urine with a specimen obtained after the woman was upright for several hours. False-positive results for protein can be due to concentrated urine, many white blood cells in the urine, or vaginal secretions with epithelial cells.

Fever, stress, and exercise can also cause transient proteinuria. Proteinuria in pregnancy should be evaluated using a hour urine collection and should not be considered pathologic until it exceeds to mg in 24 hours. Both increased after 20 weeks' gestation. Studies have shown that a 2-hour or hour collection of urine correlates with creatinine clearance and protein measured in a hour specimen. The nephritic syndrome is characterized by greater than 3 to 3.

In assessing the significance of proteinuria in pregnancy, the clinician should remember that increasing protein excretion with advancing gestation associated with known renal disease does not necessarily indicate significant progression of the disease.

Examination of urinary sediment requires a fresh specimen, ideally the first voided morning specimen. The presence of cells within a cast indicates that the cells came from the renal parenchyma. As a general guide, leukocyte casts are associated with infections or inflammatory processes, erythrocyte casts with glomerular disease, and fatty casts with nephrosis. In addition, pyuria is a common finding in renal disease. White blood cells, casts, and pyuria may be present as reaction inflammation of the glomeruli or kidney substance.

Pyuria in the absence of casts may be due to infection anywhere in the genitourinary tract. Finally, the nephritic syndrome is characterized by the presence of doubly refractile fat bodies Maltese crosses , which are visible only under polarized light.

The role of renal biopsy in pregnancy is controversial. It is potentially dangerous, especially in the presence of hypertension. Further, it has been argued that the histologic changes of glomerular disease may be obscured by the changes from pregnancy itself. In the largest study of pregnant women, Packham and Fairley 11 reported on renal biopsies and concluded that renal biopsy in the first two trimesters of pregnancy did not appear to be associated with an increased rate of complications, and in most women it provides a positive diagnosis for undiagnosed hematuria and proteinuria.

However, Kullner and coworkers 12 reported 4 hematomas in 15 antepartum biopsies and 3 hematomas in 3 postpartum biopsies; 2 of these patients required transfusion. The occurrence of complications is similar to the major complication rate of 2. Perirenal hematomas, perirenal abscess, and sepsis were considered major complications Lindheimer and associates 14 reviewed the role of renal biopsy in pregnancy and believed that biopsy should be performed only if it would change management and should be postponed until after delivery.

Postpartum renal biopsy may be useful in determining the prognosis for patients with hypertension in pregnancy. In a study of 20 postpartum renal biopsies, Gaber and Spargo 15 could distinguish between patients with glomerular endotheliosis, a reversible lesion with no long-term sequelae, and focal glomerulosclerosis, which is not reversible and indicates underlying hypertensive disease with nephrosclerosis. It is possible to categorize almost all renal problems in pregnancy using the information gained from a detailed history, urinalysis, BUN, creatinine level, and creatinine clearance.

In certain patients, renal ultrasound may provide useful additional information, particularly if renal calculi or a tumor is suspected, but may be limited secondary to the pregnancy. Renal radiographs are rarely indicated in pregnancy and pose a radiation hazard to the fetus.

If they are necessary, limiting the number of films will minimize the risk to the fetus. Computed tomography scans may aid in the diagnosis of nephritic abscesses, and magnetic resonance imaging may be helpful to rule out tumor.

Radiation exposure to the fetus should not exceed 5 rads. Cystoscopy can be performed for the usual indications. With the legalization of abortions and the use of antibiotics, the incidence of acute renal failure ARF in pregnancy has markedly decreased in developed countries secondary to a decrease in the incidence of septic abortions. A further decrease is due to improvements in prenatal care, quick recognition of the condition, and initiation of treatment of abruptio placentae and preeclampsia.

In industrialized countries, the rate of ARF is less than 0. The most common precipitating factor was hemorrhage, which included 13 cases of abruptio placentae. Severe preeclampsia or eclampsia accounted for 12 cases, and infection was the cause in 8 patients. Defined as a sudden decrease in renal function that results in retention of nitrogenous wastes, ARF can be classified as prerenal, intrinsic, or postrenal.

The causes of ARF are listed in Table 2. Prerenal conditions are the most common causes of ARF and usually result from inadequate perfusion of the kidneys. Obstetric complications of ARF include hemorrhage from placenta previa, abruptio placentae, and uterine atony Table 3. ARF from renal hypoperfusion is usually reversible within 24 to 36 hours with volume replacement and correction of the underlying cause. Most of the deaths from ARF in pregnancy are due to the underlying disease rather than the renal failure itself.

Table 2. Table 3. Preeclampsia-eclampsia HELLP syndrome Severe peripartum hemorrhage Abruptio placentae Disseminated intravascular coagulation secondary to a prolonged fetal demise Uterine atony Uterine lacerations and perforations Uterine dehiscence of cesarean scar.

Chorioamnionitis Septic abortion Puerperal sepsis. Hyperemesis gravidarum Severe vomiting from pyelonephritis. Vascular hyperactivity with preferential cortical ischemia, diminished glomerular permeability, intraluminal obstruction, back leak of luminal contents across damaged tubular epithelium, and abnormalities in prostaglandin metabolism all have been demonstrated in ATN.

There follows a recovery phase characterized by a marked diuresis; in most patients, normal renal function resumes. In addition, ATN can occur for the same reasons in the gravida as it occurs in the nonpregnant patient. It is important to distinguish between extrarenal azotemia and acute parenchymal renal failure. The former may result from congestive heart failure, hypovolemia, infection, trauma, hemorrhage, and urinary tract obstruction.

Analysis of serum and urine samples may prove helpful if the diagnosis is not clear. In ARF, volume correction should always precede the use of diuretics, with the exception of mannitol , which is a volume expander and an osmotic diuretic. Mannitol may reduce swelling of the endothelial cells and thus improve renal blood flow. If the patient is volume expanded and not hypotensive, then mannitol is contraindicated and furosemide is the diuretic of choice.

During the oliguric phase, fluids should be restricted to avoid hypertension and pulmonary edema. Life-threatening hyponatremia, hyperkalemia, and acidosis may develop rapidly; thus, electrolyte and acid-base status must be carefully monitored.

Dialysis is often the treatment of choice. During the diuretic phase of ATN, patients are at risk for electrolyte imbalance and hypovolemia. ARF may be complicated by neurologic signs such as progressive lethargy, hyperreflexia, clonus, and a positive Babinski's sign.

These signs disappear as renal function improves. Bacterial infection is a major risk and must be aggressively treated. Adequate nutritional status is important to combat infection, replace lost protein, and facilitate recovery of renal function.

Standard recommendations include restriction of protein, sodium, and potassium; however, dietary requirements vary from patient to patient and according to the level of renal function. One of the benefits of dialysis is that it allows a more flexible diet. The condition is characterized by the death of renal cortical tissue with sparing of the medulla. Its pathophysiology is uncertain. Lindheimer and colleagues 21 suggested that endothelial damage by endotoxin is followed by the formation of thrombi.

The incidence of BRCN is probably underestimated because patchy cortical necrosis with partial or almost complete recovery or renal function may be overlooked if a patient survives and the appropriate investigations are not undertaken. Abruptio placentae is the most common pregnancy complication associated with BRCN, whereas the incidence is relatively low in patients with severe preeclampsia.

BRCN should be strongly suspected if ARF develops before 30 weeks of gestation and is associated with prolonged anuria or oliguria of more than 10 days' duration. Anuria or oliguria is the rule, and urine is usually blood-stained.

Renal biopsy or selective arteriography can be used to confirm the diagnosis and distinguish between extensive and patchy cortical necrosis. Most patients with BRCN progress to chronic renal failure; before the availability of renal dialysis, the condition was usually fatal. Some patients with this disease have a slow recovery in renal function for up to 3 years after the onset and can achieve a satisfactory lifestyle without dialysis.

Preeclampsia is a syndrome characterized by hypertension and proteinuria. The disease process starts far before the appearance of any clinical signs or symptoms. Its etiology is unknown but is thought to be due to endothelial damage.

A multisystem disorder, preeclampsia has multiple effects on the kidney. It is a frequent cause of proteinuria in pregnancy.

Endotheliosis, swollen intracapillary endothelial cells in the glomeruli, is the hallmark lesion of preeclampsia in the kidney. In addition, preeclampsia may cause focal glomerular sclerosis. An increase in renal vascular resistance causes a reduction of renal blood flow. The exact etiology for the decline in renal function is unknown. After delivery, the functional decrements usually reverse quickly but can progress to ATN if treatment is not initiated at an appropriate time.

Pregnancy outcomes complicated by preeclampsia and ARF are associated with high rates of morbidity and mortality. Sibai and colleagues 18 reported outcomes in 31 pregnancies in 30 patients with renal failure; 18 women had preeclampsia and 12 had superimposed preeclampsia with existing hypertension, renal disease, or both.

All the women in the preeclampsia-only group developed ARF 1 to 5 days postpartum, whereas seven women in the other group developed ARF postpartum. Overall, gestational age at delivery was less than 30 weeks in All 18 patients in the preeclampsia-only group had ATN, and 9 required dialysis.

All patients had normal renal function within 8 weeks of follow-up. Two patients in this group died at 8 to 9 weeks postpartum after the ATN resolved. Autopsy results showed no residual renal disease. In the other group, 11 patients survived and 9 of these patients required dialysis.

Before delivery, seven of the nine had abnormal renal function. One patient who had glomerulosclerosis and ARF died 3 days after termination of her pregnancy at 16 weeks' gestation. The association of HELLP hemolysis, elevated liver enzymes, and low platelets syndrome complicated by acute renal failure does not significantly increase maternal morbidity or mortality rates. Selcuk and colleagues 23 described 39 cases of pregnancy-related ARF.

Recovery rate, maternal death rate, and fetal death rate were similar in both groups. There were no maternal deaths. An additional study revealed that subsequent pregnancies in patients who have had prior pregnancies complicated by ARF and HELLP syndrome tend to have favorable outcomes and long-term prognosis.

In conclusion, ARF is infrequent in well-managed patients with severe preeclampsia. Maternal and perinatal mortality and morbidity rates increase with the association of ARF in these patients. Early identification and proper management of ARF in patients without associated medical or obstetric complications does not result in residual renal damage. Chronic renal failure is defined as a reduction of renal mass and loss of renal reserve from an insult to the kidney.

Initially, surviving nephrons hypertrophy in number and function. This initial adaptation predisposes the remaining nephrons to sclerosis and unrelenting destruction, which can eventually lead to end-stage renal disease. Chronic renal failure has multiple etiologies; diabetes and hypertension have replaced glomerulonephritis as a major etiology.

Renal insufficiency is classified as mild, moderate, or severe. Patients with mild disease have a serum creatinine level of 1. Those with moderate renal insufficiency have a serum creatinine level of 1.

Likewise, the effects of pregnancy do not worsen renal function when mildly impaired. Early studies have reported a significant deterioration of renal function in pregnant patients with moderate renal insufficiency. However, more recent studies have shown less deterioration. In this study, end-stage renal disease was defined as a serum creatinine level of more than 6.

Women with hypertension and renal disease at the first prenatal visit were not at increased risk for preterm delivery, IUGR, or reduced fetal survival. However, hypertension in the third trimester was associated only with an increase in the rate of IUGR. Women with end-stage renal disease rarely become pregnant secondary to infrequent and irregular menstrual cycles, anovulation, and hormonal abnormalities. The frequency of conception has been reported to range from 0.

In addition, pregnancies may go unrecognized: early spontaneous abortion may be mistaken for heavy menses in women with end-stage renal disease with irregular menstruation.

Okundaye and colleagues 33 reported the largest registry of pregnant patients with end-stage renal disease. In dialysis centers, pregnancies occurred in women. In these women, 58 were started on dialysis after conception and conceived while undergoing dialysis. The outcome in women who conceived before dialysis was better than in those who conceived after beginning dialysis.

Seventy-three percent of women who started on dialysis after conception had surviving infants, compared with The remaining The authors also concluded that a lower frequency of prematurity and low birthweight was associated with conception before dialysis.

There was no statistical significance between the fetal survival rate and causes of renal failure. In addition, women who had fewer years of dialysis before conceiving tended to have a better outcome compared with those with more years of dialysis.

Lastly, there was no statistical difference in infant survival or mean gestational age of live-born infants among women with different frequencies of dialysis.

However, women who received more than 20 hours of dialysis per week had better infant survival rates and less prematurity than those receiving less than 20 hours per week. Of these, 4 infants died shortly after birth from prematurity and the other 11 showed normal development at 1 year of age. One infant was diagnosed with retrolental fibroplasias of prematurity. There were no congenital anomalies.

All showed signs of preterm labor and most were born prematurely, with the mean gestation age at delivery in the 11 surviving neonates of Survival of the neonate was associated with years of dialysis. Neonates who died of prematurity were born to women who had been receiving dialysis for more than 9 years, and the remaining who survived were born to women who had been receiving dialysis for less than 6 years. Dialysis management in a pregnant patient differs slightly from that in a nonpregnant one.

During dialysis, it is important to avoid hypotension and rapid fluctuations in intravascular volume.