In one line
Renal disease in pregnancy splits cleanly into chronic kidney disease (CKD) — where the prognosis is set before conception by eGFR, proteinuria and blood pressure — and acute kidney injury (AKI), where the job is to name the obstetric cause and decide whether the kidney or the pregnancy is the thing to treat; the recurring trap is mistaking superimposed pre-eclampsia for either.
This chapter assumes the hypertension-in-pregnancy basics and the pre-eclampsia and HELLP groundwork; it concentrates on the discrimination between subtypes, the subtype-specific management, and the judgement calls, rather than the gestational renal physiology covered there.
Assessment
The central discrimination is pre-existing CKD versus pregnancy-acquired AKI versus superimposed pre-eclampsia, because each demands a different response and they masquerade as one another (all give hypertension, proteinuria and a rising creatinine). The hypertension-in-pregnancy basics and pre-eclampsia and HELLP groundwork underpin what follows.
- Interpret renal function against pregnancy physiology, not the non-pregnant lab. GFR rises ~40–50%, so creatinine falls: a "normal-looking" creatinine of 80–90 µmol/L in the third trimester may signal substantial impairment. eGFR equations (CKD-EPI, MDRD) are not validated in pregnancy — do not quote an eGFR number; track the absolute creatinine trend and measured/estimated creatinine clearance instead.
- Stage and stratify the CKD before anything else. The pre-pregnancy eGFR band, the degree of proteinuria, and the presence of hypertension or a systemic disease (lupus, diabetic nephropathy) are the three levers that set risk — this is the TOCOS framework (see trials table). CKD stages 4–5 (eGFR <30) carry roughly a 1 in 3 chance of needing dialysis during or within a year of pregnancy.
- Quantify proteinuria correctly. Use a spot protein:creatinine (uPCR) or albumin:creatinine ratio, not 24-hour collections. The pregnancy threshold for abnormal is >300 mg/24 h — double the non-pregnant value — because physiological proteinuria rises. Pre-existing proteinuria that worsens is hard to read late in pregnancy (see the pre-eclampsia overlap below).
- AKI work-up is cause-led. Stage by KDIGO criteria, then localise: pre-renal (hyperemesis, haemorrhage, sepsis), renal (pre-eclampsia/HELLP, the pregnancy thrombotic microangiopathies — TTP, atypical HUS, acute fatty liver), or post-renal (the gravid uterus, especially over a single or transplanted kidney). Pregnancy-related AKI in low-resource settings is dominated by pre-eclampsia, sepsis and haemorrhage — the SA reality, and largely preventable.
- Angiogenic markers help where the diagnosis is muddied. Where CKD or chronic hypertension obscures the diagnosis of superimposed pre-eclampsia, a low PlGF / high sFlt-1:PlGF ratio points to placental disease rather than progressing nephropathy — the ratio is markedly higher in pre-eclampsia than in CKD, though the rule-out cut-off may need lowering when renal function is impaired.
Classifying the subtypes
What matters is not "renal disease" but the subtype, because each one carries a different mechanism, a different trajectory, and a different management lever. Three axes place every patient.
Axis 1 — CKD, by aetiology, because the cause predicts the pregnancy behaviour. Not all CKD at a given eGFR behaves the same:
- Glomerular disease (lupus nephritis, IgA nephropathy, primary glomerulonephritis). Immune-driven, proteinuric, flare-prone. The mechanism that matters is that pregnancy is a relative immune-tolerant state that can mask or unmask activity, and the kidney can deteriorate from disease activity rather than from haemodynamics alone. Lupus nephritis is the archetype: the determinant of outcome is depth and duration of remission, not the label. Quiescent for ≥6 months on a pregnancy-compatible regimen behaves well; active or recently-active disease drives flare, superimposed pre-eclampsia and fetal loss.
- Diabetic nephropathy. Hyperfiltration injury on top of pre-existing nephron loss; proteinuria often climbs steeply in the third trimester and the BP and glycaemic burden compound the renal one. The lever is pre-conception optimisation (glycaemia, BP, ACE-inhibitor withdrawal converted to a pregnancy-safe agent).
- Reflux/obstructive and structural nephropathy, single kidney, polycystic disease. Lower flare risk; the dominant risks are hypertension, UTI/pyelonephritis (and in obstruction, post-renal decompensation), and — in ADPKD — a hypertension and pre-eclampsia excess.
- Hypertensive/vascular nephrosclerosis. The renal lesion is the BP; control is renoprotection.
Axis 2 — the timing and reversibility of the insult (CKD vs AKI vs acute-on-chronic). A woman with stage 3 CKD who develops HELLP has both a fixed baseline and a reversible superimposed insult, and the management has to address each. The trap is to attribute a step-change in creatinine to "her CKD progressing" when it is an acute, treatable obstetric event.
Axis 3 — for AKI, the anatomical lesion, because that is the management. Pre-renal (restore perfusion), intrinsic (treat the specific cause — and here the microangiopathy subtype is the whole game, below), or post-renal (decompress). In the SA septic-abortion and sepsis population, renal cortical necrosis is a distinct intrinsic subtype from microvascular thrombosis of the cortex after severe sepsis, haemorrhage or abruption. Diffuse cortical necrosis usually does not recover and leaves the woman dialysis-dependent, whereas patchy necrosis can recover some function over weeks to months, so the two must be distinguished on imaging and serial function rather than declared irreversible early. Either way the management pivot is to establish maintenance dialysis and plan long-term renal replacement while tracking recovery, not to keep waiting passively.
The thrombotic-microangiopathy subtypes
Every pregnancy TMA presents with the same triad — microangiopathic haemolytic anaemia, thrombocytopenia and AKI — yet the treatments diverge completely, and the diagnosis is made on the pattern and the timing, not on a single confirmatory test (which usually returns too late to wait for). This is the discrimination on which everything else turns.
| Subtype | Distinguishing mechanism | Pattern that points to it | Treatment lever |
|---|---|---|---|
| Pre-eclampsia / HELLP | Anti-angiogenic placental disease (sFlt-1↑, PlGF↓) driving endothelial injury | Hypertension and proteinuria dominate; transaminitis prominent; platelets and LDH track the syndrome; improves within 48–72 h of delivery | Delivery. Supportive renal care; recovery is the rule |
| Acute fatty liver of pregnancy (AFLP) | Mitochondrial fatty-acid–oxidation defect (LCHAD) → microvesicular hepatic steatosis | Hypoglycaemia, marked coagulopathy with low fibrinogen, hyperammonaemia, raised bilirubin, often modest BP; Swansea criteria | Delivery + intensive supportive care (glucose, correct coagulopathy); some need liver support |
| TTP | ADAMTS13 deficiency (acquired autoantibody or congenital) → ultra-large vWF multimers | Haemolysis and neurological signs dominate; AKI often milder; profound thrombocytopenia; classically earlier in gestation; ADAMTS13 activity <10% | Plasma exchange (urgently, do not wait for the assay) ± immunosuppression; does not respond to delivery |
| Complement-mediated (atypical) HUS | Dysregulated alternative complement pathway, often unmasked postpartum | AKI dominates and is severe/oligo-anuric; haemolysis prominent; often presents or worsens postpartum; normal ADAMTS13 | Eculizumab (complement C5 blockade); plasma exchange while awaiting it; does not respond to delivery |
The most useful clinical rule: a microangiopathy that fails to improve — or that worsens — 48–72 h after delivery is not HELLP. That window re-sorts the diagnosis from "obstetric and self-limiting" to "primary TMA needing plasma exchange or complement blockade." The renal pattern helps before that: disproportionate, oligo-anuric AKI with prominent haemolysis but only modest hypertension and transaminitis argues against pre-eclampsia and toward aHUS or TTP.