Pregnancy in women with diffuse mesangial proliferative glomerulonephritis

The clinical course of 168 pregnancies in 91 women with non-IgA diffuse mesangial proliferative glomerulonephritis has been analyzed. Twenty percent (33) of pregnancies resulted in fetal loss, 18% (31) in premature delivery and 62% (105) in a term infant. Maternal renal function declined, reversibly, in 3% (5) of pregnancies and in 48% (80) hypertension developed. In 53% (89) a significant increase in proteinuria occurred in pregnancy. Fetal and maternal complications of pregnancy occurred more frequently in patients with pre-existing hypertension although differences failed to reach statistical significance (p greater than 0.01). The presence of severe vessel lesions on the diagnostic renal biopsy was associated with a significantly higher fetal loss and prematurity rate (p less than 0.0005 and p less than 0.005, respectively).     

Specific controversies concerning the natural history of renal disease in pregnancy

Whether or not pregnancy adversely affects the natural course of underlying primary renal disease, and whether fetal outcome is influenced by the type of renal disease per se are controversial issues. We retrospectively analyzed the fetal and maternal outcome in 148 women with various, biopsy-proven histological types of primary chronic glomerulonephritis (GN), including IgA GN (52 patients), membranous GN ([MGN] 20 patients), membranoproliferative type 1 GN ([MPGN] 58 patients), focal and segmental glomerulosclerosis ([FSGS] 13 patients), and minimal change nephrotic syndrome ([MCNS] 22 patients), who were pregnant (with a total of 290 pregnancies) after the clinical onset of GN, and in 104 women with reflux nephropathy (with a total of 254 pregnancies). Fetal outcome was poor in the presence of uncontrolled hypertension, nephrotic range proteinuria, and/or impaired renal function at conception or early in gestation, whatever the type of renal disease. An accelerated, more rapid than expected, worsening of maternal renal function was observed in five GN patients of whom four (two IgA, two MPGN) had serum creatinine (Scr) levels greater than 160 mumol/L (1.8 mg/dL) early in gestation, and in five patients with reflux nephropathy whose Scr at conception ranged from 180 to 490 mumol/L (2.0 to 5.5 mg/dL).(ABSTRACT TRUNCATED AT 250 WORDS)     

Influences of pregnancy on the natural course of chronic glomerulonephritis with impaired renal function]

In an attempt to clarify the influence of pregnancy on the natural course of the chronic glomerulonephritis with impaired renal function (glomerular filtration rate: GFR less than or equal to 70 ml/min), the courses of 14 pregnancies occurring in 10 patients (seven with IgA nephropathy, one with membranoproliferative glomerulonephritis, one with membranous nephropathy and one with hereditary nephropathy) were studied. In 8 patients GFR measured before pregnancies ranged from 46 to 70 ml/min and in the other two creatinine clearance estimated in the first trimester of pregnancies was 62 and 49 ml/min, respectively. The pregnancies resulted in 10 live births, one spontaneous abortion, one artificial abortion and 2 neonatal deaths. In 2 out of 10 live births fetal weight was less than 2500 g. In 3 of 11 pregnancies there was neither increase in urinary protein nor elevation of blood pressure during pregnancies, while seven (64%) had increased proteinuria during the third trimester, and 4 of them were also complicated with hypertension. In 6 of 10 patients, there was no decrease in GFR during pregnancies. In three patients GFR was decreased from 70 to 36 ml/min, 70 to 58 ml/min and 62 to 48 ml/min, respectively. However, these reductions were considered to go with the natural course of respective patients because the reduction slopes were almost the same or rather mild in comparison with those estimated before or after pregnancies. The other patient also had a transient increase in serum creatinine level during two pregnancies, but the reciprocals of serum creatinine concentration before and after the pregnanciesdeclined linearly with time. These data suggest that pregnancy might have little influence on the natural course of the chronic glomerulonephritis even if complicated with renal functional impairment defined as GFR of 70 ml/min or less.     

Successful pregnancy in primary glomerular disease

The course of 66 pregnancies was studied in 48 women with primary glomerular diseases. In all cases diagnoses were established by biopsy before pregnancy. They were: membranoproliferative glomerulonephritis in 16 patients, focal glomeruloesclerosis in 13, IgA nephropathy in 10, membranous nephropathy in seven and focal glomerulonephritis in two women. The clinical status of the nephropathy before conception was that 43 had only mild renal dysfunction, five had moderate renal insufficiency, serum creatinine (1.3 to 1.9 mg%), eight women had hypertension (150/100 mm Hg) and eight had nephrotic range proteinuria. Their clinical course was compared with a control group of 36 women with primary glomerular disease who did not become pregnant, and were matched for similar age, histological type, and status of nephropathy (renal function, blood pressure and proteinuria). After one year and at the end of the five year follow-up period, the incidence of hypertension, proteinuria, and renal failure was similar in the two groups. The fetal survival rate was 92%; 51 pregnancies ended in full-term delivery, with a mean birthweight of 3,242 +/- 320 g. There were seven pre-term deliveries (2,170 +/- 135 g), three small for gestational-age (2,340 +/- 135 g), two stillbirths and three spontaneous abortions. These patients had more pre-term deliveries (10.6%) and perinatal mortality (31%) than a normal population (5.5% and 9.6%, respectively). Blood pressure increased during pregnancy in 13 women; in 10 it was reversible, and in four it persisted after delivery. Ten gravidas developed increased proteinuria (reversible in six of them) and two others developed permanent impairment of renal function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thin basement membrane nephropathy in pregnancy

There are several published series of pregnancy in patients with nonimmunoglobulin A mesangial proliferative glomerulonephritis (most of whom have thin basement membrane nephropathy [TBMN]). The aim of the present study was to review the maternal and fetal outcomes of pregnancy in women with TBMN. The medical and obstetric histories of 86 women with TBMN and their 182 pregnancies (one twin) were reviewed. Data were collected retrospectively in 164 pregnancies (90%) and prospectively in 18 pregnancies (10%). Hypertension (alone or with proteinuria) developed in 15 unmonitored pregnancies (9%), and proteinuria alone developed in the third trimester in 2 pregnancies (1%). Hypertension was more common in the prospectively monitored pregnancies (6 pregnancies, 33%). In all, there were 174 live births (95%), and all fetal deaths occurred in the first and second trimesters in the absence of maternal complications. However, all the mothers of the 4 small for gestational age babies had been hypertensive. In TBMN, maternal hypertension, prematurity, and small for gestational age rates did not exceed those in the normal population. Overall, pregnancy in women with TBMN does not appear to be attended by a significantly increased maternal or fetal risk.     

Acute renal failure and nephrotic syndrome due to membranoproliferative nephritis during the second trimester of pregnancy

We report the case of a patient with acute renal failure and nephrotic syndrome during the second trimester of an otherwise uncomplicated pregnancy. Despite pregnancy, percutaneous renal biopsy was performed to evaluate the etiology, showing Type I membranoproliferative glomerulonephritis. Two therapeutic options were considered: pregnancy termination, suggested by the gynecologists, and our proposal of starting steroid therapy, in order to reduce proteinuria and improve renal function. The patient refused pregnancy termination. She received i.v. methylprednisolone boluses, followed by maintenance oral prednisone and aspirin, with prompt acute renal failure resolution and reduced proteinuria. At Week 34 + 5 days of gestation, cesarean section was performed, without intra- and postoperative complications both for mother and newborn. Clinical maternal and fetal outcomes were excellent. One-year follow-up showed normal renal function and absence of proteinuria. Lacking guidelines concerning treatment of acute renal failure due to primary nephropathy in pregnancy, we consider this case of interest for our decision-making process and for the favorable outcome.     

妊娠并发肾病综合征的临床研究

目的 探讨妊娠并发肾病综合征患者的妊娠结局及肾功能的变化。 方法 回顾性调查我院2003年至2007年间59例妊娠并发肾病综合征患者的临床资料,包括患者出现肾病的时间、尿蛋白量、血浆白蛋白、Scr、血尿酸、血压;胎儿存活率、死亡率、早产率、出生体质量;以及孕妇产后随访蛋白尿、肾功能和血压情况。采用Logistic回归方法,分析影响妊娠患者的肾脏转归及胎儿预后的危险因素。 结果 孕妇出现蛋白尿孕周平均为（20.35±9.40）周,尿蛋白量（24 h）3.5~15.0 g,中位数5.1 g;血浆白蛋白10~28 g/L,中位数22.5 g/L;Scr 32~825 μmol/L,中位数84 μmol/L;血尿酸196~793 μmol/L,中位数385.5 μmol/L。妊娠高血压综合征发生率为75%,其中先兆子痫占55.5%。胎儿存活率72.9%（43/59）,其中早产占76.7%（33/43）;低体质量儿占62.8%（27/43）。产后50%患者持续肾病综合征。24例原有慢性肾炎,其中75%患者蛋白尿较怀孕前有不同程度的增加。38例伴有肾功能受损,其中36.8%患者产后肾功能受损加重,23.7%进入终末期肾衰竭;其中80%发生在Scr≥265 μmol/L的患者。89%患者产后持续高血压。Logistic 回归结果提示,孕期高尿酸血症（P=0.018,OR=1.012）和Scr升高（P=0.039,OR=1.005）是孕妇产后肾功能受损加重的危险因素。高尿酸血症（P=0.012,OR=1.006）也是胎儿死亡的危险因素。 结论 妊娠并发肾病综合征患者的胎儿存活率低,其中高尿酸血症是威胁孕妇和胎儿的首要危险因素。     

Pregnancy and renal transplantation

Ovarian dysfunction, anovulatory vaginal bleeding, amenorrhea, high prolactin levels, and loss of libido are the causes of infertility in women with chronic renal failure. After renal transplantation, endocrine function generally improves after recovery of renal function. In this study we retrospectively evaluated the prepregnancy and postdelivery renal function, outcome of gestation, as well as maternal and fetal complications for eight pregnancies in eight renal transplant recipients between November 1975 and March 2003 of 1095 among 1425. Eight planned pregnancies occurred at a mean of 3.6 years posttransplant. Spontaneous abortion occured in the first trimester in one case. One intrauterine growth retardation was observed with a full-term pregnancy; one intrauterine growth retardation and preterm delivery; one preeclampsia with preterm delivery and urinary tract infection; and one preeclampsia with preterm delivery and oligohydramnios. The mean gestation period was 35.5 +/- 3.0 weeks (31.2 to 38.0). Pregnancy had no negative impact on renal function during a 2-year follow-up. No significant proteinuria or acute rejection episodes were observed. Among the seven deliveries, no congenital anomaly was documented and no postpartum problems for the child and the mother were observed. Our study suggests that successful pregnancy is possible in renal transplant recipients. In cases with good graft function and absence of severe proteinuria or hypertension, pregnancy does not affect graft function or patient survival; however, fetal problems are encountered such as intrauterine growth retardation, low birth weight, and preeclampsia.     

Pregnancy and lupus nephritis.

Family planning and pregnancy are important and usually problematic issues for a young woman with lupus nephritis. Moderate renal insufficiency and previous use of alkylating cytotoxic drugs are associated with decreased fertility. Oral contraceptives containing synthetic estrogens are contraindicated in women with active lupus nephritis, uncontrolled hypertension, history of thromboembolic diseases or high levels of antiphospholipid antibodies. Mild flares of systemic lupus erythematosus (SLE) are common during pregnancy, severe renal flares and permanent impairment of renal function are uncommon. The outlook of pregnancy for women with lupus nephritis is usually favourable if the disease (both renal and nonrenal) has been quiescent for at least 6 months before pregnancy, and if, at conception, serum creatinine is less than 140 micromol/l, proteinuria less than 3 g/24 h and blood pressure controlled. The risk of fetal loss is, however, at least 2-3 times higher than in the normal population and pre-eclampsia, prematurity and fetal growth retardation frequently complicate these pregnancies. Especially poor fetal outcome is associated with antiphospholipid antibodies. Pregnancies in women with lupus nephritis require intense fetal and maternal surveillance.     

Histological features of IgA glomerulonephritis as predictors of pregnancy outcome

116 pregnancies undertaken by 70 women with IgA glomerulonephritis and their diagnostic renal biopsies have been reviewed. An IgA diffuse mesangial proliferative lesion with superimposed focal and segmental proliferative lesions (IgA FSP) on diagnostic renal biopsy was associated with a greater incidence of maternal complications than IgA diffuse mesangial proliferative glomerulonephritis with no superimposed lesions (IgA DMP) and IgA diffuse mesangial proliferative glomerulonephritis with superimposed focal and segmental hyalinosis and sclerosis (IgA FSHS) (p less than 0.025). Patients with severe vessel lesions had a significantly greater incidence of fetal loss than those with only mild to moderate lesions (p less than 0.025).     

Unilateral renal vein occlusion in rats

To study the relationship of renal vein thrombosis to membranous glomerulonephritis with the nephrotic syndrome, we attempted to simulate the former by occluding to 0.5 mm one renal vein in rats. Although increased proteinuria did occur during the first 3 days after such occlusion, there was little difference from control animals in the amount of proteinuria thereafter, up to 46 days, and no evidence of membranous glomerulonephritis by light, immunofluorescent, or electron microscopy.     

Pregnancy Outcomes After Kidney Donation

The outcome of pregnancy in kidney donors has generally been viewed to be favorable. We determined fetal and maternal outcomes in a large cohort of kidney donors. A total of 2102 women have donated a kidney at our institution; 1589 donors responded to our pregnancy surveys; 1085 reported 3213 pregnancies and 504 reported none. Fetal and maternal outcomes in postdonation pregnancies were comparable to published rates in the general population. Postdonation (vs. predonation) pregnancies were associated with a lower likelihood of full-term deliveries (73.7% vs. 84.6%, p = 0.0004) and a higher likelihood of fetal loss (19.2% vs. 11.3%, p < 0.0001). Postdonation pregnancies were also associated with a higher risk of gestational diabetes (2.7% vs. 0.7%, p = 0.0001), gestational hypertension (5.7% vs. 0.6%, p < 0.0001), proteinuria (4.3% vs. 1.1%, p < 0.0001) and preeclampsia (5.5% vs. 0.8%, p < 0.0001). Women who had both pre- and post-donation pregnancies were also more likely to have these adverse maternal outcomes in their postdonation pregnancies. In this large survey of previous living donors in a single center, fetal and maternal outcomes and pregnancy outcomes after kidney donation were similar to those reported in the general population, but inferior to predonation pregnancy outcomes.     

IgA glomerulonephritis and pregnancy

One hundred and sixteen pregnancies in 70 women with a biopsy-proven diagnosis of IgA glomerulonephritis have been analysed. Thirty percent (35) of the fetuses died, 22% (26) were premature and 44% (52) were full term. Maternal renal function declined during pregnancy in 26% (30) and in 2% (2) this was irreversible post-partum. Hypertension developed in 52% (61) of the pregnancies and in 13% (15) this was irreversible. Increased proteinuria was recorded in 62% (74) of the pregnancies. Fetal loss in pregnancies taking place after biopsy diagnosis was lower (16%) than those in which biopsy was performed either during or following the pregnancy (36%).     

Outcome of Pregnancy in Women with Glomerular Diseases

Over the last 16 years the evolution of 24 pregnancies in 17 women with biopsy-proven glomerular disease was analyzed. The underlying renal histology was IgA nephropathy in 8 cases, lupus nephritis in 7, mesangiocapillary glomerulonephritis type I in 1, and focal segmental glomerulosclerosis in 1. All but 2 had normal renal function before conception and 3 were hypertensive. Fetal survival rate was 75%. There were 6 preterm deliveries (33.3%), 3 newborns small for gestational age (17%), 1 stillbirth, and 5 therapeutic abortions. The perinatal mortality was 5.5%. De novo hypertension occurred in 8 pregnancies (33.3%). In 11 pregnancies (46%) increased proteinuria was diagnosed and in 6 (25%) a decline in maternal renal function was recorded. Permanent impairment of renal function was seen in 2 women with renal insufficiency before conception. Maternal hypertension and renal function impairment were associated more frequently with obstetric complications. In conclusion, pregnancy is safe for normotensive mothers with glomerular diseases and normal renal function. Hypertension and impaired renal function at conception seem to carry increased risk for mothers and fetuses. Low-dose immunosuppressive treatment during pregnancy is not harmful for the fetus.     

Glomerular disease and pregnancy. A study of 123 pregnancies in patients with primary and secondary glomerular diseases

The clinical course of 123 pregnancies in 86 patients with biopsy-proven glomerular diseases have been studied. In 35 women the onset of nephropathy occurred during pregnancy. No complications were observed in more than half of the pregnancies. In the others, one third of the complications were obstetrical or fetal accidents, one third were renal manifestations (hypertension or deterioration of renal function) and one third were both causes. The lowest incidence of complications was observed in patients with membranous nephropathy and the highest in membranoproliferative glomerulonephritis patients. There were 6 spontaneous late abortion, 6 stillbirths and 5 neonatal deaths. 17 deliveries were preterm and 7 fetuses were small for gestational age. Hypertension appeared in 24 pregnancies, in 13 of which it was reversible and related to superimposed preeclampsia and in 11 it persisted after delivery (5 of these 11 pregnancies were in patients with IgA nephropathy). Renal function deteriorated in 10 cases during pregnancy. The deterioration was reversible in 6 and progressive in 4 (2 of whom had membranoproliferative glomerulonephritis). It is suggested that in most patients pregnancy does not change the natural history of glomerular disease.     

The kidney in hypertensive pregnancies--victim and villain.

Many changes in renal function occur in normal pregnancy. Without a proper understanding of these changes, routine clinical investigations may easily be misinterpreted. Women with preeclampsia have further alterations in renal function and, in occasional cases, develop acute renal failure. Understanding of abnormal renal physiology and hormonal changes in these women allows the clinician to interpret biochemical tests appropriately and make proper use of vasodilator therapy with careful attention to volume homeostasis. Women who undertake pregnancy with a primary renal disease, most commonly glomerulonephritis or reflux nephropathy, have a higher risk of adverse fetal and maternal outcomes. Awareness of these risks provides a basis for proper preconceptual counseling, as well as careful monitoring of maternal blood pressure and renal function and fetal growth during such pregnancies. These strategies will optimize the chances of a successful pregnancy outcome for both mother and baby.     

Pregnancy outcome after renal transplantation

AIMS: The aim of our study was to evaluate the frequency and the outcome of pregnancies in renal transplant recipients at our center. METHODS: This study involved the retrospective analysis of 405 childbearing female renal recipients for presence of risk factors, the outcome of pregnancy, and maternal and fetal complications. RESULTS: Fourty-four pregnancies occurred in 41 patients (10.8%). Mean age at transplantation was 23.6 +/- 6.3 years (range, 12-38 years). Only in 5 pregnancies were there no risk factors. In 13 (29.5%) pregnancies, the previous creatinine level was >1.5 mg/dL, in 16 (36.45%), proteinuria was >500 mg/24 hours; 29 (65.9%) were hypertensive; 14 (31.8%) had a time between transplantation and pregnancy less than 2 years (mean time, 35.5 +/- 30.9 months; range, 3-120 months). The outcomes were 27 (61.4%; 11 term and 16 premature delivery) successful pregnancies, 6 (13.6%) spontaneous abortions, 10 (22.7%) therapeutic abortions, and 1 (3.2%) fetal death. Pre-eclampsia occurred in 9 (20.4%) pregnancies and eclampsia in 1 (2.2%). The mean weight of the offspring was 2195 +/- 490 g (range, 1300- 2980 g). There were 2 cases of acute fetal distress and 1 oligodramnios. Median creatinine level was 1.0 (range, 0.4-3.0) mg/dL before conception and 1.2 (range, 0.7-9.0) mg/dL 6 month after pregnancy (P <.001). The long-term patient and graft survival rates were similar for pregnant versus nonpregnant recipients in the childbearing age. CONCLUSION: Most pregnancies were successful, although the premature delivery rate was high (36.4%). Only 5 conceptions occurred in the absence of risk factors. Pregnancy did not impair the patient and graft survival during long-term follow-up.     

Contrasting response to cyclosporin in refractory nephrotic syndrome

We studied the effects of cyclosporin A (CsA), given for three months, in 14 patients with nephrotic syndrome refractory to treatment with prednisone and/or other immunosuppressants. CsA was given in a starting dose of 6 mg/kg and plasma through levels (RIA) were kept between 50 and 150 ng/ml. Diagnosis included: idiopathic membranous glomerulonephritis (n = 6), focal segmental glomerulosclerosis (n = 3), minimal change disease (n = 3) and membranoproliferative glomerulonephritis (n = 2). Three patients with non-immunologically mediated nephrotic syndrome due to Alport's syndrome were studied as well. Considering all patients and diagnostic groups together, proteinuria decreased from 9.0 +/- 4.3 to 4.7 +/- 3.8 g/24 h during CsA treatment (mean +/- SD; p less than 0.01). However, serum creatinine increased from 121.8 +/- 60.5 to 150.4 +/- 64.6 mol/l (p less than 0.01) and glomerular filtration rate as estimated by 24-hour creatinine clearance fell from 85.5 +/- 33.7 to 72.1 +/- 37.2 ml/min (p less than 0.05). When compared to other diagnostic groups, fractional excretion of protein, i.e. protein excretion corrected for changes in glomerular filtration rate, fell only in IMGN (ANOVA, p less than 0.05). We conclude that CsA reduced proteinuria in patients with refractory nephrotic syndrome. In the majority of these patients this reduction could be due to a renal hemodynamic, rather than an immunomodulatory effect of the drug. Only in IMGN the latter action of the drug may be of importance.     

Maternal hemodynamics and pregnancy outcome in women with prior orthotopic liver transplantation

The aim of this study is to evaluate the hemodynamics and pregnancy outcome of women with prior orthotopic liver transplantation. Hemodynamic measurements by Doppler technique were performed on pregnant subjects with prior orthotopic liver transplantation. Maternal characteristics, renal function, pregnancy complications, delivery indications, delivery mode, and neonatal outcomes were evaluated. Six pregnancies occurred in 5 women after orthotopic liver transplantation at the University of Washington Medical Center (Seattle, WA) between 1991 and 1999. Four of the 6 pregnancies were complicated by chronic hypertension, fetal growth restriction, and preterm delivery. Two pregnancies had worsening hypertension characterized by vasoconstriction in the second trimester despite antihypertensive therapy. These 2 subjects were administered cyclosporine for maintenance immunosuppression and had greater mean arterial pressures preconception and in the first trimester than the other subjects. One of these pregnancies resulted in fetal demise at 25 weeks' gestation. The other subject was delivered at 28 weeks' gestation for nonreassuring fetal status and superimposed preeclampsia. All pregnancies were complicated by renal insufficiency; however, the 2 subjects with poor obstetric outcome had preconception serum creatinine levels greater than 1.5 mg/dL and creatinine clearances less than 40 mL/min. Pregnancies complicated by second-trimester vasoconstriction and moderate renal insufficiency are at risk for preeclamspia, fetal growth restriction, and fetal demise. Good obstetric outcome can occur in women with mild renal insufficiency and well-controlled chronic hypertension. Improved hypertensive control preconception may decrease the risk for preeclampsia and poor obstetric outcome.     

Clinicopathological study of membranous glomerulonephritis in patients with rheumatoid arthritis]

Of 103 patients with membranous glomerulonephritis proved by renal biopsy, 11 (10.7%) had rheumatoid arthritis. Nine of these 11 patients received systemic treatment with anti-rheumatic remedies including gold, D-penicillamine and bucillamine. Two others were administered only token of nonsteroidal antiinflammatory drugs. Renal function of the patients was well maintained and within normal limits. Four patients showed nephrotic syndrome, while mild to moderate proteinuria was found in the other 7. Hematuria was minimal to mild, and it was not a major symptom. Six patients resolved proteinuria completely and 2 patients incompletely after discontinuation of chrysotherapy. Nine cases of the membranous lesion in patients with rheumatoid arthritis were stage 1. Thus it was often difficult to identify the glomerular change only by light microscopy. IgA nephropathy and AA amyloidosis were associated in one patient respectively. Our data lead us to conclude that chrysotherapy would cause membranous lesions, but rheumatoid arthritis itself also induce membranous glomerulonephritis.