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Introduction
Chronic renal insufficiency occurs in 0.03–0.2% of all pregnancies. Although rare, these parturients have a significantly increased maternal and fetal morbidity and mortality and can present a significant challenge to the anaesthetist. The management of this high-risk group of patients is often complicated and is supported by little evidence. It requires an understanding of the physiological changes of pregnancy, the optimization of existing management, close monitoring of both mother and fetus, and early involvement of obstetricians, nephrologists, neonatologists and anaesthetists, with early intervention as required.
Renal insufficiency in pregnancy may be classified into three categories. These include known pre-existing renal disease diagnosed prior to the pregnancy, sub-clinical chronic renal disease unveiled by the pregnancy or new-onset disease that develops during the pregnancy. Although general principles can be applied to the management of these patients, the causes, associated co-morbidities and prognosis of these patients may differ greatly.
It is important to consider both the impact of renal insufficiency upon maternal and fetal outcome, and the impact of a pregnancy upon the short- and long-term course of chronic kidney disease. These patients have an increased risk of pregnancy-induced hypertension, pre-eclampsia, preterm delivery, intrauterine growth restriction and perinatal mortality. The demands of pregnancy may result in a transient, and sometimes a permanent decline in renal function.
The assessment of renal function in pregnancy
Pregnancy itself results in anatomical and physiological changes in the renal system (See Chapter 1). Changes in water metabolism, extracellular fluid volume regulation, acid–base regulation and the renal handling of electrolytes, protein and glucose result in altered ‘normal ranges’ of typical laboratory values. These values continue to change from the first to the second and third trimesters. This complicates the diagnosis, assessment and surveillance of renal insufficiency. The gold standard for measuring and therefore monitoring renal function remains inulin clearance, but it is difficult to perform. Creatinine clearance measured with a 24-hour urine collection is the most well-validated method for approximating glomerular filtration rate (GFR). Formulaic estimations of GFR lack validity in pregnancy.
GFR and creatinine clearance typically increase by 40–65% and serum creatinine concentrations fall. It has been suggested that the upper limit of serum creatinine concentration should approximate 85, 80 and 90 mol/L in the first, second and third trimesters, respectively. A blood urea nitrogen concentration of >13 mg/dL may also indicate renal insufficiency in pregnancy.
The associated increase in urinary protein excretion also results in an altered definition of proteinuria during pregnancy of greater than 300 mg/day (correlating to 1+ on urine dipstick) compared to a non-pregnant value of 150 mg/day.
For these reasons the usual prepregnancy NICE classification of the stages of chronic kidney disease (Table 20.1) is difficult to apply during pregnancy, yet it remains a useful tool when considering a patient’s prepregnancy values. Traditionally parturients have been stratified into mild impairment serum creatinine <125 µmol/L, moderate 125–250 µmol/L and severe >250 µmol/L.
| Stagea | GFR (mL/min/1.73 m2) | Description |
|---|---|---|
| 1 | <i</i>>≥90</i</i>> | Normal or increased GFR with other evidence of kidney damage |
| 2 | 60–89 | Slight decrease in GFR with other evidence of kidney damage |
3a 3b | 45–59 30–44 | Moderate decrease in GFR with or without other evidence of kidney damage |
| 4 | 15–29 | Severe decrease in GFR with or without other evidence of kidney damage |
| 5 | <15 | Established renal failure |
a Use suffix (p) to denote presence of proteinuria (protein creatinine ratio ≥ 50 mg/mmol)
Chronic kidney disease in pregnancy
There are many causes of CKD in women of childbearing age, all of which will be seen in pregnancy. The most common include diabetic nephropathy, hypertensive nephropathy, chronic glomerulonephritis, systemic lupus nephritis, polycystic kidney disease and chronic pyelonephritis among many rarer causes. The underlying pathology and its associated systemic co-morbidities, as well as the systemic manifestations of chronic renal impairment itself provide significant challenges to the anaesthetist. The risk of adverse outcome to either mother or fetus does not appear to be related to the specific underlying disorder, but to the degree of renal impairment and the presence or absence of hypertension.
The effect of pregnancy on kidney disease
Pregnancy can exacerbate pre-existing renal disease and, in some cases, can cause irreversible deterioration in renal function. Adverse outcomes tend to relate to the degree of maternal renal function and blood pressure control. The pathogenesis is not clearly evident, but altered immune function, increased inflammation, endothelial dysfunction and platelet aggregation resulting in microvascular thrombi have all been implicated.
Proteinuria and associated peripheral oedema worsens in approximately 50% of cases and hypertension may develop or worsen in 25% of cases. These features frequently resolve post partum.
Evidence suggests that patients with a normal or only mildly reduced GFR and a serum creatinine concentration less than 132 μmol/L have a less than 10% risk of a permanent decline in renal function as a consequence of pregnancy. The presence of hypertension in this group of patients gives a poorer prognosis. Patients with moderate renal insufficiency, a serum creatinine concentration between 132 and 255 μmol/L, are likely to experience an initial fall in serum creatinine concentration as GFR increases, but this will continue to rise up to and beyond the baseline by the third trimester. These patients have approximately a 50% risk of a permanent reduction in GFR and a 10% risk of developing end-stage renal disease within 12 months of delivery. This figure may increase to 50% if there is associated uncontrolled hypertension. In severe renal failure the likelihood of conception and carrying a fetus to term is very low. Up to 40% of these patients will require dialysis. It is important to note that pregnancy may result in immune sensitization and potential difficulties for future donor matching should renal transplant be indicated. CKD also increases the risk of urinary tract infection, which in turn may cause a rapid deterioration in renal function. Co-existing pre-eclampsia is also associated with subsequent progression to end-stage renal disease.
The prevention of deterioration of renal function in these patients relies upon close surveillance by a multidisciplinary team, monthly serial monitoring of maternal renal function, early detection and treatment of asymptomatic bacteruria and aggressive treatment of maternal hypertension. Although the management of hypertension is important, many antihypertensives are contraindicated in pregnancy. Labetalol, α-methyldopa and nifedipine are considered safe. Preterm delivery may be necessary to preserve long-term kidney function.
The effect of kidney disease on pregnancy outcomes
A large systematic review demonstrated a fivefold higher incidence of maternal morbidity and twofold higher incidence of fetal morbidity in the presence of maternal CKD.
Patients with CKD are more likely to develop gestational hypertension, pre-eclampsia and eclampsia. Preterm deliveries are around twice as common and there is a recognized association with intrauterine growth restriction and still birth. Again the risks of maternal and fetal complications seem to be directly proportional to the degree of renal impairment and are further increased by the presence of uncontrolled hypertension. Patients with mildly reduced GFR and well-controlled blood pressure have very favourable outcomes. However, there may be as high as a 20–30% and 40% increased risk of pre-eclampsia in patients with moderate and severe renal insufficiency, respectively. In this situation, the diagnosis of pre-eclampsia is often difficult. The presence of hypertension at the time of conception increases the risk of fetal loss by up to tenfold. Significant proteinuria is also associated with an increased risk of preterm delivery.
These patients may require weekly antenatal reviews, with close monitoring of blood pressure to allow the early diagnosis and treatment of co-existing pre-eclampsia, in addition to aggressive management of pre-existing hypertension. Fetal growth and wellbeing should be monitored.
The systemic manifestations of chronic kidney disease
Chronic kidney disease is a multisystem disorder with far-reaching systemic manifestations. These may occur irrespective of the underlying pathology and have implications in the antenatal, intrapartum and perioperative anaesthetic management of these patients (Table 20.2).
| Cardiovascular system | Hypertension, ischaemic heart disease, peripheral vascular disease, aortic calcification, calcific valvular heart lesions, uraemic pericarditis, cardiomyopathy |
| Respiratory system | Potential difficult airway, pulmonary oedema, atelectasis and infection |
| Haematological system | Normochromic normocytic anaemia, platelet dysfunction Low/normal platelet count |
| Immune system | Immunosuppression, risk of hepatitis B and C |
| Gastrointestinal system | Delayed gastric emptying, reduced gastric pH, malnutrition |
| Neurological system | Myoclonus, encephalopathy, convulsions, autonomic neuropathy, peripheral neuropathies |
| Endocrine system | Impaired glucose tolerance, tendency towards hypothermia, reduced fertility |
| Fluid and electrolytes | Hyperkalaemia, hyponatraemia, hypocalcaemia, renal osteodystrophy, hypermagnesaemia |
| Acid–base regulation | Chronic metabolic acidosis, poor buffering capability |
| Pharmacokinetic changes | Reduced protein binding Accumulation of renally excreted drugs |
Common underlying chronic renal disorders
Diabetic nephropathy
Diabetes, gestational or otherwise, is one of the most common diseases occurring in pregnancy. Diabetic nephropathy most frequently occurs in those in whom type 1 diabetes has been present for over 10 years and is characterized by proteinuria, hypertension and a reduced GFR. Patients with good glycaemic control, microalbuminuria, well-preserved renal function and well-controlled blood pressure are likely to have a successful outcome. However, patients with overt nephropathy preconception are at increased risk of pre-eclampsia, fetal growth restriction, preterm delivery and irreversible deterioration in renal function.
The principles of management include preconception assessment of nephropathy, patient counselling and optimization of glycaemic control. Hypertension should be controlled with labetalol, α-methyldopa or calcium-channel blockers such as nifedipine. Close monitoring should continue throughout pregnancy. Good intrapartum glycaemic control and fluid balance are important.
Systemic lupus nephritis
Systemic lupus erythematosus (SLE) is a common autoimmune disorder in women of childbearing age. The associated nephritis presents unique challenges in pregnancy.
Lupus nephritis may have spontaneous exacerbations during pregnancy, which are associated with a 75% chance of fetal loss. The presence of active disease at the time or within six months of conception and the duration of disease significantly increase the risk of an exacerbation during pregnancy. It remains unclear whether pregnancy itself is a risk factor for lupus flares.
A lupus flare is characterized by deteriorating renal function, hypertension, worsening proteinuria and thrombocytopenia, making it difficult to distinguish from pre-eclampsia, a condition which may also co-exist. Presentation prior to 20 weeks’ gestation or the presence of hypocomplementaemia, urinary red blood cell casts, a typical rash, arthritis or serositis make lupus nephritis more likely. The mainstay of the management is general supportive care and immunosuppression with steroids and azathioprine, which may exacerbate pre-eclampsia. When stabilization is not achieved, delivery may be indicated.
SLE is associated with the presence of antiphospholipid antibodies, which increase the risk of both lupus flares and thrombotic events such as deep vein thrombosis, pulmonary embolism, myocardial infarction and stroke. Patients should undergo preconception antibody screening. When antibodies are present patients should receive aspirin prophylaxis with additional heparin if there is a history of thrombotic events.
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