O36
Alport’s/thin basement membrane disease, pregnancy and proteinuria
Hall M1, Kapoor D2, Ferraro A1, Wallace S2
Nottingham Renal and Transplant Unit1 and Department of Maternal Medicine2, Nottingham
University Hospitals
INTRODUCTION: Physiological changes of pregnancy include increased proteinuria to
approximately twice baseline levels. Increased renal blood flow can only account for a
proportion of this increase. Changes in glomerular capillary permeability and trans-capillary
hydrostatic pressure are postulated to account for the rest. Women with chronic kidney disease
(CKD) may commence pregnancy with increased protein excretion as a result of their
underlying disease. For some, pregnancy can induce nephrotic range proteinuria, nephrotic
syndrome and associated complications. We observed that some women with glomerular
collagen disorders (Alport’s syndrome (AS) or thin basement membrane (TBM) disease) had
particularly pronounced increases in proteinuria. Disease-specific pregnancy outcomes for
women with AS/TBM are not well reported. The aim of the analysis is to test the hypothesis
that these conditions lead to more pronounced increases in proteinuria than other kidney
diseases.
METHODS: 7 patients with AS/TBM, 7 patients with other glomerular diseases and 7 patients
with non-glomerular CKD were identified from the local Obstetric-Renal service. NonAS/TBM patients were matched for age and baseline creatinine. Baseline values were obtained
from preconception laboratory reports. Proteinuria was quantified from spot urine samples as
protein:creatinine ratios (P:CR). Women without P:CR quantification but urine dipstick analysis
negative for proteinuria were arbitrarily assigned a P:CR of 10mg/mmol. The increase in
proteinuria was calculated as the ratio between peak pregnancy proteinuria and baseline
proteinuria. Differences between the three groups were compared with one way ANOVA and
Bonferroni post-hoc analysis. Values are presented as mean±standard deviation.
RESULTS: AS/TBM, other glomerular and non-glomerular CKD patients were well matched
for age (27.4±6.3, 27.8±2.2, 23.9±2.6 years respectively, p=0.19), baseline creatinine (75±24,
91±32, 74±14µmol/l respectively, p=0.41) and estimated glomerular filtration rate (CKD-EPI
98±30, 82±27, 102±20 ml/min/1.73m2 respectively, p=0.4). Baseline proteinuria was similar in
women with AS/TBM and other glomerular diseases (238±161 vs 103±109 mg/mmol, p=0.14)
and higher than in those with non-glomerular diseases (9.6±0.8 mg/mmol, p=0.005).
The increase in proteinuria during pregnancy was greater for women with AS/TBM than for
women with other glomerular diseases (4.9±3.6 vs 1.3±0.8, p=0.04) and non-glomerular
diseases (1.6±1.6, p=0.05). Nephrotic range proteinuria (P:CR>300mg/mmol) during pregnancy
was found in 6 (86%) women with AS/TBM, 2 (29%) women with other glomerular diseases
and no women with non-glomerular diseases.
CONCLUSION: Women with AS/TBM are at high relative and absolute risk of pronounced
increases in proteinuria during pregnancy. They should be counselled that this may occur and
that prophylactic low molecular weight heparin may be indicated to minimise venous
thromboembolic events. Further follow-up data of this cohort will be used to identify the impact
of these changes on renal disease progression, and maternal and fetal pregnancy outcomes.
Marked changes in circulating angiogenic and antiangiogenic factors have been identified
during pregnancy and these are implicated in the pathogenesis of proteinuria in pre-eclampsia.
We postulate that changes in these factors particularly affect women with AS/TBM and
warrants future study.