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Angiotensin-converting enzyme (ACE) gene plays an important role in pathogenesis of lupus nephritis (LN) with kidney failure with or without kidney replacement therapy (KRT). Our study aims to investigate the distribution of genotypes and alleles I/D of the ACE gene and the correlation between the ACE gene and clinical manifestations of kidney failure in LN patients with and without KRT.
A case-control study was conducted at Cho Ray Hospital from 12/2021 to 07/2023 enrolling 208 LN patients. All patients were met the criteria of American College of Rheumatology in 1997 or the Systemic Lupus Internation Collaborating Clinics in 2012 and classified into 3 groups: (1) Group 1 (Control- No kidney failure): 71 patients, (2) Group 2 (Kidney failure without KRT): 55 patients, (3) Group 3 (Kidney failure with KRT): 82 patients. Lupus nephritis was defined as 24-hour proteinuria > 0.5g with or without red cell cast. Kidney failure was defined as estimated glomerular filtration rate (CKD-EPI) on admission ≤ 60 ml/min/1.73m2. Maintenance dialysis and pregnancy were excluded. Clinical thrombotic microangiopathy (TMA) was scored based on 6 features, in which each feature was 1 point, including anemia (haemoglobin ≤ 12g/dL if female and ≤ 13 g/dL if male), platelet < 150 G/L, D-dimer > 600 UI/L, lactate dehydrogenase > 600 UI/L, haptoglobin < 40mg/dL, schistocyte > 1%. ACE genotypes were determined by the polymerase chain reaction method. Distribution of alleles and genotypes was compared using the χ2-test with 2x2 contingency tables. Binary logistic regression was used to determine the association of the ACE gene and clinical parameters in LN patients. p< 0.05 was considered significant. Interaction was tested between I/D polymorphism and mean arterial pressure (MAP).
In clinical features, LN patients in group 3 had higher MAP, higher proportion of clinical TMA score > 3 points, higher lupus activity (SLEIDAI score) than those in control group (p<0.05). Mean 24-hour proteinuria was 3g and there was no significant difference between 3 groups (p>0.05). In histological features (80 patients), the percentages of class III-VI LN, acute tubular injury, tubulo-interstitial inflammation, renal TMA were higher in group 3 than control (p<0.05). The skewed distribution between 3 groups were observed in allele D (0.204, 0.355 and 0.372 in group 1, 2 and 3 respectively, p=0.003) and DD genotype (0.028, 0.146 and 0.122 in group 1, 2 and 3 respectively, p=0.05). There was a strong association between I/D polymorphism and LN with kidney failure and those with KRT in multivariate analysis adjusting for age and gender. Other factors conferred susceptibility of kidney failure with KRT and kidney failure in LN were MAP, clinical TMA score >3 (Table 2). No interaction between MAP and ACE gene was found.
Allele D and DD genotype were predominant in LN and kidney failure with KRT patients. I/D polymorphism of ACE gene could be associated with susceptibility of kidney failure with or without KRT in LN patients.