11 Liz Lightstone Centre for Inflammatory Disease, Department of Medicine, Imperial College London, London, UK Providing care for women with underlying renal disease contemplating pregnancy or those already pregnant requires that the obstetrician has up‐to‐date knowledge about pregnancy physiology, antenatal care and the technology for fetal surveillance. It is essential to appreciate the need for multidisciplinary teamwork in a centre with all the necessary facilities for dealing with high‐risk patients and their babies. It is estimated that chronic kidney disease (CKD) affects up to 6% of women of childbearing age in high‐income counties, and has been estimated to affect 3% of pregnant women. This chapter focuses on CKD, women on dialysis and kidney transplant recipients, aiming to provide the busy clinician with information for counselling and judicious decision‐making. The basic components should be analysis of risks as well as provision of health education and advice plus any interventions that might be considered helpful, all united under the banner of that much‐used word ‘counselling’ [1]. The multidisciplinary team has to decide what is important so that active preparation for pregnancy is tailored to each woman’s needs, with her being encouraged to involve her partner so that all the implications can be discussed, including potential areas of disagreement, even whether infertility treatment, if needed, would be made available. All healthcare professionals looking after women of childbearing age with kidney disease need to raise the issue of her plans, or not, for pregnancy. It may not be apparent to the woman that her kidney disease poses any issues for her or a baby. Once prompted, aside from what the team wants to discuss and achieve for the woman and her partner, she herself usually has four straightforward questions. Most women focus on the third question but it is essential to ensure that all relevant information and even harsh realities are passed on, based on fact not anecdote. She must understand the risks and the need to improve her own knowledge, so that she can best use the guidance and support to make any necessary changes in her behaviour, attitude and medication(s). However, knowledge, and even understanding, of the risks may not be sufficient to ensure the patient makes the changes because many other factors influence her behaviour. Even when there is an element of self‐management (perhaps best exemplified with dialysis and/or diabetes) this will also be affected by the woman’s repertoire of beliefs, skills, intuition and motivation and not just her so‐called knowledge, however gained. The key is a strong, unwaivering, positive and supportive relationship with the team that allows pre‐pregnancy advice to be included in the overall care agenda as a goal‐orientated process. Thus a planned pregnancy is one that is desired well before conception, occurs when contraception is discontinued and where the woman attempts to achieve optimal health beforehand. Even if some of the answers are not favourable, a woman, being an autonomous adult, may still choose to plan for (or proceed with) a pregnancy in an effort to re‐establish a normal life in the face of chronic illness [2]. Indeed some women may not seek advice until already pregnant. Occasionally, there may be ethical dilemmas regarding the clinician’s duty of care for women who ignore advice; interestingly, there are studies that have differentiated ‘healthy’ and ‘pathological’ levels of assumed risk and which have tried to understand the psychology of women who pursue parenthood despite big risks to their own health and the unborn child [3]. The renal tract undergoes marked anatomical, haemodynamic, tubular and endocrine changes as part of the systemic upheaval of maternal adaptation to pregnancy [4,5]. The kidneys enlarge because both vascular volume and interstitial space increase but there is no accelerated renal growth nor morphological alterations akin to compensatory renal hypertrophy. The calyces, renal pelves and ureters dilate markedly, invariably more prominent on the right side, seen in 90% of women. Glomerular filtration rate (GFR), measured as 24‐hour creatinine clearance (Ccr), increases by 6–8 weeks’ gestation. Serum creatinine (Scr) and serum urea (Surea), which average 70 µmol/L and 5 mmol/L respectively in non‐pregnant women, decrease to mean values of 50 µmol/L and 3 mmol/L during pregnancy. Values for Scr of 80 µmol/L and Surea of 6 mmol/L, which are acceptable in the non‐pregnant state, are suspect in pregnancy. At term, a 15–20% decrement in Ccr occurs, which affects Scr minimally. The 24‐hour urinary total protein excretion (TPE) increases in normal pregnancy, and up to 300 mg per 24 hours can be regarded as normal [6]. So‐called significant proteinuria (TPE >300 mg per 24 hours) may correlate with a protein concentration of 30 mg/dL in a ‘spot’ urine sample. Timed urine collections are no longer required since proteinuria can be reliably monitored with the use of ‘spot’ urine protein/creatinine ratios that equal 30 mg/µmol or more. A woman may lose up to 50% of her renal function and still maintain Scr below 125 µmol/L because of hyperfiltration by the remaining nephrons; however, if renal function is more severely compromised, then further small decreases in GFR will cause Scr to increase markedly []. In women with CKD, whilst the pathology may be both biochemically and clinically silent, the internal milieu may already be disrupted. Most individuals remain symptom‐free until GFR declines to less than 25% of normal, and many serum constituents are frequently normal until a late stage of disease. However, degrees of functional impairment that do not appear to disrupt homeostasis in non‐pregnant individuals can jeopardize pregnancy. Because a normal creatinine does not necessarily reflect normal kidney function, for the past few years it has become accepted practice to classify renal function in non‐pregnant patients using estimated GFR (eGFR; units, mL/min per 1.73 m2) calculated from a formula based on Scr adjusted for age, gender and race (Black African descent or not). The so‐called Modified Diet in Renal Disease (MDRD) formula was developed in the USA in a multiethnic population of women and men with moderate renal impairment and, most importantly, an eGFR below 60 mL/min per 1.73 m2. The classification recognizes five stages of CKD (Table 11.1). In non‐pregnant populations, eGFR is much less reliable in patients with CKD stages 1 and 2 because of the poor correlation with actual GFR when it exceeds 60 mL/min [10]. In fact over 95% of women with underlying CKD becoming pregnant do have an actual GFR of 60 mL/min or more. Table 11.1 Stages of CKD classified according to the US National Kidney Foundation. Sources: Davison et al. [5], Rich‐Edwards et al. [11], National Kidney Foundation [12], Davison & Lindheimer [13], and Imbasciati et al. [14]. eGFR, estimated glomerular filtration rate. Unlike many prediction formulas, the MDRD equation is not individualized for body surface area and is therefore theoretically attractive for use in the obstetric population in whom increased surface area is not a reflection of increased muscle mass and therefore of increased Scr. However, reports to date have not borne this out and during pregnancy the MDRD fomula substantially underestimates GFR compared with the gold standard of inulin clearance [15,16]. An important clinical concern deriving from the fact that eGFR tends to underestimate true GFR is that its use might signal to the clinician an exaggerated deterioration in GFR, perhaps promoting unnecessary delivery. Therefore, the use of the MDRD equation during pregnancy to estimate GFR in women who have known renal impairment prior to conception or who develop renal complications during pregnancy cannot be recommended. The same applies for the CKD‐Epi formula [17]. In addition, the Cockroft–Gault formula, and many others, are inaccurate in pregnancy and there is disagreement about using cystatin C to monitor renal function [18]. However, in prospective studies of women with known renal function prior to pregnancy, outcomes are now being related to pre‐pregnancy CKD stages based on eGFR rather than serum creatinine. It might seem that a system based on GFR would be superior to one based on Scr and perhaps the database in the literature should be converted to this new CKD classification [13]. We would argue almost certainly not, as the great majority of pregnant women are those with mild disease (CKD stages 1 and 2) and, as mentioned already, the formulas for eGFR in women whose values are anticipated to be above 60 mL/min in the non‐pregnant state are unreliable, though better with use of CKD‐Epi. Furthermore, the traditional system has been easy to disseminate and is familiar to non‐nephrology specialists. Whilst defending the use of Scr it must nevertheless be mentioned that very small women may present with normal or mildly elevated Scr, and clinicians should be suspicious of abnormal function if they see a pregnant woman with a serum creatinine greater than 80 µmol/L. The basic question for a woman with CKD must be: is pregnancy advisable? The timing of the pregnancy depends on whether the CKD is caused by relapsing remitting disease such as systemic lupus erythematosus (SLE) or is progressive and function likely to decline over time, for example adult polycystic kidney disease (APKD). In the latter scenario, it is clear that if all else is stable, then sooner is better as with time function will only worsen and risks increase. If the former, then disease should be inactive for several months prior to trying to conceive as active disease is associated with worse outcomes. Many women still present pregnant without prior counselling and then the question must be whether pregnancy should continue (Table 11.2). Table 11.2 Pre‐pregnancy considerations in chronic kidney disease. Obstetric and long‐term renal prognoses differ in women with different levels of dysfunction (for recent reviews of pregnancy and CKD, see Hladunewich et al. [21] and Webster et al. [22]). Counselling is based on three functional parameters: the degree of renal insufficiency (Table 11.3), the presence or absence of hypertension and the underlying kidney disease. Until recently, all the data on outcomes of pregnancy in women with CKD were based on retrospective data, which traditionally and arbitrarily classified renal insufficiency solely by pre‐pregnancy Scr: 125 µmol/L or less as descriptive of ‘mild’ insufficiency, 125–250 µmol/L as ‘moderate’ insufficiency, and above these levels as severe insufficiency [23]. Their use has been the mainstay of pre‐pregnancy counselling for over 25 years, consistently showing that normotensive women with intact or only mildly decreased but stable renal function generally do very well, experiencing more than 95% live births, about 75% of which are appropriate for gestational age. These excellent statistics also reflect a literature that has shown constantly improving perinatal outcomes from the 1980s onwards, indicative of the marked advances in both antenatal and neonatal care [24–31]. With mild insufficiency there is an increased incidence of superimposed pre‐eclampsia or late pregnancy hypertension, as well as increased proteinuria, exceeding the nephrotic range (3 g per 24 hours) in 50% of women in the second half of pregnancy. Pregnancy does not appear to adversely affect the course of the CKD. However, there are exceptions to this optimistic outlook [31,32]. Indeed, the earliest prospective study of women with baseline CKD stages 3–5 covering 23 years assessed the rate of decline of maternal renal function during pregnancy in 49 white non‐diabetic women with CKD stages 3–5 before pregnancy (eGFR <60 mL/min per 1.73 m2 pre‐pregnancy) to average 39 months after delivery [14]. This multicentre Italian network effort confirmed earlier observations that such women have complicated pregnancies with poor perinatal outcomes as well as an accelerated decline in renal function [33]. The main conclusion was encouraging because while the group as a whole lost function during pregnancy, the rate of loss was not affected by pregnancy. Also, 95% of the fetuses survived, albeit many were born preterm and/or growth restricted. The best outcomes were to women whose pre‐pregnancy eGFR was between 60 and 40 mL/min per 1.73 m2, corresponding to Scr values between 125 and 141–150 µmol/L or proteinuria less than 1 g/day. On the other hand, women with eGFR below 40 mL/min per 1.73 m2 and proteinuria above 1 g/day had poorer outcomes, the combination resulting in worse outcomes than either factor alone. Although these women developed renal failure faster than other groups, it was not possible to determine if pregnancy was a causal factor. Table 11.3 Pre‐pregnancy kidney function (Scr) in CKD patients with estimates for obstetric outcome and renal functional loss. Source: Lindheimer & Davison [34]. Estimates are based on a 26‐year literature review of pregnancies (1984–2010) which attained at least 24 weeks’ gestation. ESRF, end‐stage renal failure. *Compared with pre pregnancy serum creatinine. Recently however, prospective data from the TOCOS study [35] have suggested even women with CKD stage 1 (eGFR >90 mL/min and Scr probably much lower than 125 µmol/L) without baseline hypertension, proteinuria above 1 g/day, or systemic disease before pregnancy had an increased risk of a combined adverse outcome (preterm, neonatal intensive care or small for gestational age) (odds ratio, OR 1.88; CI 1.27–2.79) versus women with no CKD. Additionally, the risks for preterm delivery rose further for women with CKD stage 1 associated with baseline hypertension (OR 3.42)/proteinuria (OR 3.69)/systemic disease (OR 3.13). Thus, all women with CKD should be considered high risk and be assessed for risk of adverse pregnancy outcomes. Prognosis is poorer when there are greater degrees of renal dysfunction (reviewed in Hladunewich et al. [21] and Webster et al. [22]). With moderate impairment, live births still approach 90%, but the incidence of pre‐eclampsia, fetal growth restriction and/or preterm delivery exceeds 50%. With severe dysfunction, outlook is more drastically curtailed. Although there is a paucity of data for analysis in both these categories, what has become obvious is that a cut‐off Scr of 250 µmol/L is too high for moderate impairment, with 180 µmol/L more appropriate, and thus there is a tendency to designate these patient groups ‘moderate to severe’ (Tables 11.3 and 11.4). This literature is slowly increasing and the message could not be clearer: hypertension is common by term (60%) as is significant proteinuria (50%) as well as deterioration in renal function (at times rapid and substantial) and although infant survival rates are good (80–90%), rates of premature delivery (60%) and fetal growth restriction (40%) underscore the very high potential for obstetric complications in these women [36–39]. Not previously so obvious are the facts that 30–50% of women with moderate insufficiency experience functional loss more rapidly than would be expected from the natural course of their renal disease and that poorly controlled hypertension might be a harbinger of poor outcome [40–43]. Once Scr rises above 250 µmol/L there are even bigger risks of accelerated loss of renal function, and even terminating the pregnancy may not reverse the decline (Table 11.3). Table 11.4 Pre‐pregnancy kidney function (Scr) in CKD patients with estimates for obstetric complications and outcome and renal functional loss. Estimates are based on literature from 1985 to 2009, with all pregnancies attaining at least 24 weeks’ gestation (Davison & Winfield, unpublished data). Modified and supplemented from Williams & Davison [8]. Note that from more recent analyses of women with severe CKD it is now apparent that an Scr cut‐off of 250 µmol/L is too high a level for ‘moderate’ renal impairment, a cut‐off of 180 µmol/L now being recommended [1,13]. Temporary or acute dialysis has been advocated during pregnancy in the face of overall deterioration in renal function (especially when Surea exceeds 20 mmol/L and/or there is refractory hyperkalaemia), severe metabolic acidosis, pulmonary oedema responding poorly to diuretics, and danger of volume overload with heart failure [5,31,39,44]. Dialysis may increase the chance of successful outcome by ‘buying time’ for fetal maturation but it does not arrest the inexorable decline in renal function, ultimately to end‐stage failure. In trying to avoid extreme prematurity in this way, it has to be asked whether such life‐threatening effects on the mother’s renal prognosis can be justified. Nevertheless, the awareness by some women of progress in antenatal care and neonatal provision encourages them to anticipate good outcomes and they will say that they are prepared to take a chance and even seek assisted conception in the face of their infertility. Of importance in all the current controversies is that the literature that forms the basis of our views is primarily retrospective, with most patients only having mild dysfunction and women with severe to moderate disease being limited in number. Confirmation of guidelines and prognoses therefore requires adequate prospective trials. The prospective TOCOS study only had 10 women with advanced CKD (pre‐pregnancy eGFR <30 mL/min per 1.73 m2); however, 90% of these had adverse pregnancy outcomes and 80% had severe adverse outcomes [35]. Additionally, 20% progressed to a worse stage of kidney function at the end of pregnancy. These women ideally will have had pre‐pregnancy counselling to ensure optimal timing, that disease is quiescent, medications and blood pressure control optimized and that they understand the risks of pregnancy. Once pregnant, they must be seen as early as possible. Thereafter assessments should usually be performed at least every 4 weeks until 28 weeks’ gestation and then every 1–2 weeks depending on the clinical circumstances [8,45]. Table 11.5 Chronic renal disease and pregnancy. Women with certain types of CKD face particularly increased risks with pregnancy, including those with lupus and especially those with prior lupus nephritis. In addition, women with scleroderma and classical periarteritis nodosa do poorly (particularly when there is marked renal involvement and associated hypertension and/or pulmonary hypertension) and thus should be counselled to avoid pregnancy. Furthermore, there is some disagreement about whether pregnancy adversely influences the natural history of IgA nephropathy, focal segmental glomerulosclerosis and reflux nephropathy. It seems likely that prognosis with these renal lesions is actually similar to that of women with mild impairment in general, provided pre‐pregnancy function is preserved and high blood pressure absent (Table 11.5). Reflux nephropathy often presents for the first time during pregnancy as women have recurrent UTIs and hypertension. Ultrasound may reveal scarred kidneys, hydronephrosis and function may or may not be normal. It is important to make the diagnosis not just to ensure optimal care of the woman during pregnancy but so that her baby will be appropriately screened in the first year of life – there is a strong genetic influence on the presence of reflux and early diagnosis may prevent renal scars [46]. Because SLE most commonly affects women of childbearing age and since about 60% of people with SLE will develop lupus nephritis, this is one of the commoner forms of renal disease seen in pregnant women. Recent data from a prospective cohort of 385 women with well‐controlled SLE (with or without prior lupus nephritis, proteinuria <1 g/day, creatinine <106 µmol/L and taking less than 20 mg oral prednisolone at baseline) showed, in the absence of baseline hypertension or a lupus anticoagulant, that 81% of the women had successful pregnancies and flares were infrequent [47]. Moroni et al. [48] reported recently on 71 pregnancies in 61 Italian women all of whom had prior or active lupus nephritis and had undergone pre‐pregnancy counselling. The majority (78.9%) were in complete remission and the rest had mild active lupus nephritis. Flares were seen in 19.7% of women and all responded to treatment. Pre‐eclampsia was seen in 8.4% (a figure very consistent with the Mayo group systematic review published in 2010 [49]) and HELLP syndrome (haemolysis, elevated liver enzymes, low platelets) in 2.8%; both pre‐eclampsia and HELLP were predicted by prior lupus nephritis, longer disease duration and baseline hypertension. Fetal loss occurred in 8.4%, preterm delivery in 28.2%, and 16.4% of babies were small for gestational age (SGA). Importantly, the use of the antimalarial hydroxychloroquine appeared to significantly reduce the probability of having an SGA baby [50]. In addition, it is known from other studies that hydroxychloroquine almost certainly reduces the risk of congenital heart block and neonatal lupus in babies born to mothers with anti‐Ro antibodies. The following recommendations apply to all CKD patients. If renal function deteriorates significantly at any stage of pregnancy, then reversible causes, such as UTI, volume depletion or electrolyte imbalance (occasionally precipitated by inadvertent diuretic therapy), should be sought. Near term, as in normal pregnancy, a decrease in function of 15–20%, which affects Scr minimally, is permissible. Failure to detect a reversible cause of a significant decrement may be an indication for early delivery. However, this will depend on the underlying renal disease, whether progression of renal impairment was expected and whether dialysis during pregnancy is an option. When proteinuria occurs and persists, but blood pressure is normal and renal function preserved, pregnancy can be allowed to continue under closer scrutiny. With nephrotic‐range proteinuria, prophylactic low‐molecular‐weight heparin is needed and should be continued for 6 weeks after delivery. The use of acute dialysis has been mentioned earlier. The conventional dividing line for obstetric hypertension has been 140/90 mmHg. Most of the specific risks of hypertension in pregnancy appear to be related to superimposed pre‐eclampsia (see Chapter 7). There is confusion about the true incidence of superimposed pre‐eclampsia in women with CKD. This is because the diagnosis cannot be made with certainty on clinical grounds alone: hypertension and proteinuria may be manifestations of the underlying CKD, and chronic hypertension alone has an increased pre‐eclampsia risk fourfold that of normotensive pregnant women. Treatment of mild hypertension (diastolic blood pressure <95 mmHg in the second trimester or <100 mmHg in the third) was not previously necessarily considered mandatory during normal pregnancy, but many would treat women with CKD more aggressively, believing that this preserves kidney function. The CHIPS study brought the obstetric community into closer alignment with the renal community by demonstrating fewer episodes of severe hypertension in the women assigned to the ‘tight’ control group (achieved blood pressure 133/85 mmHg). In non‐pregnant women with renal disease, particularly those with proteinuric renal disease, the target blood pressure would be less than 130/80 mmHg so this would seem to be a reasonable target now in pregnant women [19]. Medications such as methyldopa, calcium channel blockers, labetalol and hydralazine are safe in pregnancy. Angiotensin‐converting enzyme (ACE) inhibitors and angiotensin receptor blockers should not be prescribed and even if patients were taking either of these in early pregnancy (to continue the so‐called renal protection from before pregnancy), they should not be continued or recommended beyond the early first trimester. We advise patients with minimal proteinuria to switch from ACE inhibitors or angiotensin receptor blockers before pregnancy. In those women with heavy proteinuria and progressive renal decline, the benefit of continued renal protection probably outweighs the low risk of early first trimester exposure. In those women we advise cessation as soon as pregnant in order to avoid months pre‐pregnancy with no renal protection. Recent data suggest that the excess congenital abnormalities attributed to ACE inhibitors may in fact all be explained by hypertension rather than the medication [51]. ACE inhibitors and angiotensin receptor blockers are contraindicated (except in the rare instance of a woman having scleroderma) beyond the first trimester because of the risk of a fetopathy. Serial evaluation of fetal well‐being, with regular assessment of fetal growth, amniotic fluid and Doppler, is essential. In the absence of fetal or maternal deterioration delivery should be at or near term. If complications do arise, the judicious moment for intervention might be determined by fetal status (see Chapter 28). Regardless of gestational age, most babies weighing more than 1500 g survive better in a special care nursery than a hostile intrauterine environment. Planned preterm delivery may be necessary if there is impending intrauterine fetal death, if renal function deteriorates substantially, if uncontrollable hypertension supervenes, or if pre‐eclampsia occurs. Obstetric considerations should be the main determinant for delivery by caesarean section. Experience with renal biopsy in pregnancy is relatively sparse, mainly because clinical circumstances were considered to rarely justify the risks [5,9]. However, there are now case series reporting safety in selected cases in early pregnancy. Biopsy should be considered in the first trimester if there is a suspicion of rapidly progressive glomerulonephritis or a new presentation of nephrotic syndrome. In women with known renal disease (e.g. prior lupus nephritis or previous membranous glomerulonephritis), clinical judgement may well allow a biopsy not to be undertaken in pregnancy. However, ‘blind’ treatment with steroids or other immunosuppressants is not without risk and having a firm diagnosis is very helpful. Beyond 18–20 weeks most would not biopsy but use clinical status and blood tests to judge most likely diagnosis and treatment. In reality, biopsy during pregnancy remains a relatively infrequent event [52] but it is imperative that women presenting with new‐onset proteinuria in early pregnancy are not lost to follow‐up post partum as they may well need a biopsy in due course to ensure the correct diagnosis is made and appropriate therapy given. When renal biopsy is undertaken immediately after delivery in women with well‐controlled blood pressure and normal coagulation indices, the morbidity is certainly similar to that reported in non‐pregnant patients. Readers are referred to earlier sections for advice regarding the impact of pregnancy on CKD. Whilst the recent TOCOS study suggests significant impact even of CKD stage 1 on renal outcomes, in the majority of women with normal eGFR, pregnancy does not cause deterioration or otherwise affect rate of progression of CKD beyond what might be expected in the non‐pregnant state, provided pre‐pregnancy kidney dysfunction was minimal and/or hypertension is absent or very well controlled before pregnancy [24,31,33,44]. An important factor in long‐term prognosis could be the sclerotic effect that prolonged gestational renal vasodilatation might have in the residual (intact) glomeruli of the kidneys of these women. The situation may be worse in a single diseased kidney, where more sclerosis has usually occurred within the fewer (intact) glomeruli. Although the evidence in healthy women and those with mild renal disease argues against hyperfiltration‐induced damage in pregnancy, there is little doubt that in some women with moderate, and certainly severe, dysfunction there can be unpredicted, accelerated and irreversible renal decline in pregnancy or immediately afterwards. It is also now well recognized that both CKD and pre‐eclampsia influence remote prognosis in both groups in terms of cardiovascular disorders and end‐stage renal failure but there is debate about whether the superimposition of pre‐eclampsia on CKD hastens progression to end‐stage status [53–57]. It seems that pre‐eclampsia is not a risk factor (‘marker’ is a better term) for progression (see Chapter 7) but can lead to a stepwise decrease in renal function in those with underlying renal disease. The TOCOS study suggested strongly that, across all levels of baseline renal function, a proportion of women will develop worse renal function post partum. Despite reduced libido and relative infertility, women on long‐term dialysis do conceive and must therefore use contraception if they wish to avoid pregnancy [14,21,58,59]. Although conception is not common (an incidence of 1 in 200 patients has been quoted), its true frequency is unknown because many pregnancies in dialysis patients probably end in early spontaneous abortion. The high therapeutic abortion rate in this group of patients (which has decreased from 40% in the 1990s to under 15% today) still suggests that those who become pregnant do so inadvertently, probably because they are unaware that pregnancy is possible. Recent data on improved fertility, likely due to normalization of the hypothalamic–pituitary–gonadal axis, as evidenced by the return of regular menstrual cycles [60] with increased dialysis, have persuaded some to consider increasing dialysis hours to assist conception in those women who wish to become pregnant and who have no prospect of a renal transplant in their fertile years.
Renal Disease
Pre‐pregnancy assessment
What the woman wants to know
What the patient needs to understand
Normal pregnancy
Chronic kidney disease
Renal impairment and the prospects for pregnancy and afterwards
Assessment of renal impairment and its implications for CKD in pregnancy
Estimated GFR
Stage
eGFR (mL/min per 1.73 m2)
1
Kidney damage (structural or proteinuria) with normal or even increased GFR
≥90
2
Kidney damage (structural or proteinuria) with mild GFR decrease
60–89
3
Moderate GFR decrease
30–59
4
Severely low GFR
15–29
5
Kidney failure
<15 or dialysis
eGFR versus Scr
Renal pathology under consideration
Good general health
Review and optimize pre‐pregnancy drug therapy
Diastolic blood pressure ≤80 mmHg or well‐controlled hypertension with ‘safe’ medication(s)
Scr ideally <125 µmol/L, at least ≤180 µmol/L, and very concerning from 180 to ≤250 µmol/L
No or minimal proteinuria
‘Well‐controlled’ comorbidities (e.g. diabetes mellitus, infections)
Relevance of obstetric history
Renal status Dysfunction
Scr (µmol/L)
Problems in pregnancy (%)
Successful obstetric outcome (%)
Permanent loss of kidney function* (>25% increment in Scr*) (%)
ESRF within 1 year post partum (%)
Mild
≤125
26
96
<2
Moderate
≥125
42
95
15
1
Severe
≥180
80
74
52
38
Scr (µmol/U)
Fetal growth restriction (%)
Preterm delivery (%)
Pre‐eclampsia (%)
Perinatal deaths (%)
Loss of >25% renal function
Pregnancy (%)
Persists post partum (%)
End‐stage failure in 1 year (%)
≤125
25
30
22
1
2
–
–
125–180
45
70
40
6
40
20
3
≥180
70
>90
60
12
70
55
35
Temporary dialysis
Antenatal strategy and decision‐making
Renal disease
Clinical watchpoints
Chronic glomerulonephritis and focal segmental glomerular sclerosis (FSGS)
In the absence of hypertension and abnormal renal function, most of these women will have normal pregnancies though probably have a higher risk of late hypertension and pre‐eclampsia. In the presence of hypertension and/or renal impairment, there may be accelerated loss of renal function possibly due to podocyte stress during pregnancy
IgA nephropathy
Some cite risks of sudden escalating or uncontrolled hypertension and renal deterioration. Most note good outcome when renal function is preserved
Chronic pyelonephritis (infectious tubulointerstitial disease)
Bacteriuria in pregnancy, recurrent urinary tract infections (often requiring prophylactic antibiotics) and frequent hypertension
Reflux nephropathy
Some have emphasized risks of sudden escalating hypertension and worsening of renal function. Consensus now is that results are satisfactory when pre‐pregnancy function is only mildly affected and hypertension is absent. Vigilance for urinary tract infections is necessary
Urolithiasis
Ureteral dilatation and stasis do not seem to affect natural history, but infections can be more frequent. Stents have been successfully placed and sonograpically controlled ureterostomy has been performed during gestation
Polycystic kidney disease
Outcomes largely predicted by baseline function and hypertension. Women should be advised to have their pregnancies before they have lost function
Diabetic nephropathy
Proteinuria is likely to increase significantly during pregnancy and if nephropathy is advanced, salt and water retention may predominate. Most women with diabetes do not have overt nephropathy during their childbearing years; however, this is becoming more common as women have children later in life and the rates of type 2 diabetes in younger women increase. Increased frequency of infections, oedema or pre‐eclampsia
Human immunodeficiency virus with associated nephropathy (HIVAN)
Renal component can be nephrotic syndrome or severe impairment. Need to ensure anti‐retroviral treatment is optimised pre‐pregnancy
Systemic lupus erythematosus
Prognosis is most favourable if disease is in remission 6 months before conception, the woman does not have lupus anticoagulant, and if non‐white does not have hypertension at baseline. If the mother has anti‐Ro antibodies she should be offered fetal echocardiography at 18/40 to look for early signs of congenital heart block
Systemic vasculitis (granulomatous or microscopic polyangiitis)
If in remission will have little impact on pregnancy. However, flares can occur and if severe may mandate early termination of pregnancy to allow adequate treatment of aggressive renal disease. Rare
Scleroderma
If onset during pregnancy, there can be rapid overall deterioration. Reactivation of quiescent scleroderma can occur during pregnancy and after delivery
Previous urologic surgery
Depending on original reason for surgery, there may be other malformations of the urogenital tract. Urinary tract infection is common during pregnancy and renal function may undergo reversible decrease. No significant obstructive problem, but caesarean section might be necessary for abnormal presentation or to avoid disruption of the continence mechanism if artificial sphincters or neourethras are present
After nephrectomy, solitary and pelvic kidneys
Pregnancy is well tolerated. Might be associated with other malformations of the urogenital tract. Dystocia rarely occurs with a pelvic kidney
Impact of underlying renal disease
Renal function
Blood pressure
Fetal surveillance and timing of delivery
Role of renal biopsy in pregnancy
Long‐term effects of pregnancy in women with renal disease
Patients on dialysis
Dialysis and the prospects for pregnancy and afterwards
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