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Objective In this study, we trace the changes in the clinical and histological pattern of IgA nephritis (IgAN) in Singapore as it has evolved over 4 decades and compare the clinical, demographic, histological, and renal outcome of patients with IgAN from the 1st decade and the 4th decade. Materials and methods This is a retrospective study of all histologically proven IgAN diagnosed between 1976 and 2018. Clinical, laboratory, and histological characteristics between the 1st and the 4th decade, including treatment which could influence the disease progression and renal outcome of these two groups, were compared. We used the Oxford classification to compare the renal biopsy changes for these 2 decades as we were able to retrieve 125 renal biopsy tissues for the 1st cohort of IgAN studied in the 1970s for the comparative study. Results The commonest clinical presentation throughout the first 3 decades was asymptomatic hematuria and proteinuria (63, 52, and 49%, respectively). In the 4th decade, nephrotic syndrome (31%) was the commonest followed by asymptomatic hematuria and proteinuria (30%), hypertension (21%), and chronic renal failure (11%). The data showed that treatment can modify the Oxford MEST - Crescent scores. Renin-angiotensin system (RAS) blockers modified the S scores, immunosuppressants modified the T and C scores, and combination therapy with RAS blockers and immunosuppressants modified the E, S, and T scores. Conclusion The Oxford MEST classification offers a robust and expressive classification for early and late disease progression with respect to the development of end-stage renal disease (ESRD). E and S seem to be indices of continuing disease activity with progressive glomerulosclerosis, probably still amenable to therapy, but T was a predictive indicator for those destined for ESRD and no longer amenable to therapy.

Background and Aims Nephrotic syndrome is associated with hypercholesterolemia, while its treatment, often involving high-dose glucocorticosteroids, may cause hyperglycemia. Proprotein convertase subtilisin /kexin type 9 (PCSK9) regulates plasma cholesterol and is associated with post-transplant diabetes. Although a potential therapeutic target in nephrotic syndrome, the relationships between PCSK9 and lipid parameters are not well established. We aimed to characterize serum PCSK9 and metabolic parameters among individuals with nephrotic syndrome. Method Single-center prospective cohort study of non-diabetic adults newly-diagnosed with nephrotic syndrome and subsequently treated with immunosuppressant. Fasting serum PCSK9 was measured using ELISA at diagnosis. Clinical history, blood pressure, body mass index (BMI), waist-to-hip ratio (WHR) and biochemistry (fasting glucose and lipid, HbA1c and fasting serum PCSK9) were obtained at diagnosis and at 3 months during immunosuppression therapy. Spearman’s correlation was used to evaluate for associations between PCSK9 and glycemic and lipid parameters. Results Among 15 adults with nephrotic syndrome, the majority was female (60%) and Chinese (80%). Median age was 40 (IQR 26, 51) years. The most frequent diagnoses were minimal change disease or focal segmental nephrosclerosis (n=7) and lupus nephritis (n=5); the minority had IgA nephropathy, membranous nephropathy or vasculitis. At diagnosis, median eGFR was 97.9 (59.5, 120.9) ml/min/1.73 m2, UPCR 7.6 (6.1, 10.4) g/g, LDL-cholesterol 4.6 (3.1, 6.7) mmol/L and fasting serum PCSK9 317.6 (276.8, 470.1) ng/ml. PCSK9 correlated positively with hypertriglyceridemia (r=0.55, p=0.03) at baseline. Most patients (n=14, 93%) were treated with prednisolone (monotherapy or in combination with other immunosuppressant) and 1 received tacrolimus monotherapy. At 3 months, the majority (n= 11, 73%) had achieved clinical remission. Fasting serum PCSK9 was higher at 3 months [median 430.6 (283.1, 496.0) ng/ml] compared to baseline, although the difference was not statistically significant. At 3 months, PCSK9 correlated positively with age (r=0.58, p=0.03), LDL-cholesterol (r=0.90, p=0.04) and change in BMI (r=0.72, p=0.01). Conclusion PCSK9 is associated with metabolic parameters at diagnosis and during the treatment course in patients with nephrotic syndrome treated with immunosuppressant.

A genome-wide association study in Japan identified the C-C chemokine receptor type 6 gene (CCR6) as associated with rheumatoid arthritis (RA). This finding has not been validated in other Asian populations. A case-control study involving 996 subjects, comprising 440 controls and 556 RA patients, was done to determine their anticyclic citrullinated peptide (anti-CCP) antibody status and CCR6 polymorphism (rs3093024) genotype. Three hundred eighty-seven patients were anti-CCP positive and 153 anti-CCP negative. Logistic regression showed that allele A was likely to increase the risk of developing RA among females via a recessive model (odds ratio [OR]=1.55, 95% confidence interval [CI]=1.01, 2.39), whereas the risk effect appeared to be reduced among males via an additive model (OR=0.60, 95% CI=0.42, 0.85). Considering only subjects who are anti-CCP positive, allele A increased RA risk among females via a recessive model (OR=1.68, 95% CI=1.07, 2.64) but decreased the risk among males via an additive model (OR=0.59, 95% CI=0.39, 0.89). We showed that CCR6 polymorphism was a risk factor among females but a protective factor among males. Functional studies are warranted to unravel the pathophysiological relevance of the gene variant and other linked variants with RA.

Background and Purpose— Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare congenital disorder caused by mutation in the ROBO3 gene. It is characterized by absent horizontal eye movements with progressive scoliosis developing in childhood and adolescence. To our knowledge, both diffusion tensor imaging evaluation in HGPPS patients who present with stroke and truncating stop codon mutation in the ROBO3 gene have yet to be reported. Summary of Case— We present a man with HGPPS who experienced a left pure motor stroke as a result of a left corona radiata infarct on diffusion-weighted imaging. Diffusion tensor imaging tractography confirmed the presence of uncrossed corticospinal tracts, accounting for the ipsilateral deficit. He was also found to possess a novel ROBO3 stop codon mutation on genetic testing. Conclusions— Patients with HGPPS may present with stroke symptoms on the ipsilateral side of the infarct in view of uncrossed corticospinal tracts. Truncating mutation in ROBO3 may provide additional pathophysiologic insights.