Long term outcome of immunoglobulin A (IgA) nephropathy: A single center experience.

INTRODUCTION: IgA nephropathy (IgAN) has a heterogeneous presentation and the progression to end stage renal disease (ESRD) is often influenced by demographics, ethnicity, as well as choice of treatment regimen. In this study, we investigated the long term survival of IgAN patients in our center and the factors affecting it. METHODS: This study included all biopsy-proven IgAN patients with ≥ 1year follow-up. Patients with diabetes mellitus at diagnosis and secondary IgAN were excluded. Medical records were reviewed for demographics, clinical presentation, blood pressure, 24-hour urine protein, serum creatinine, renal biopsy and treatment received. The primary outcome was defined as combined event of 50% estimated glomerular filtration rate (eGFR) reduction or ESRD. RESULTS: We included 130 (74 females; 56 males) patients of mean age 38.0 ± 14.0 years and median eGFR of 75.2 (interquartile range (IQR) 49.3-101.4) ml/min/1.73m2. Eighty-four (64.6%) were hypertensive at presentation, 35 (26.9%) had nephrotic syndrome and 57 (43.8%) had nephrotic range proteinuria (NRP). Median follow-up duration was 7.5 (IQR 4.0-13.0) years. It was noted that 18 (13.8%) developed ESRD and 34 (26.2%) reached the primary outcome. Annual eGFR decline was -2.1 (IQR -5.3 to -0.1) ml/min/1.73m2/year, with median survival of 20 years. Survival rates from the combined event (50% decrease in eGFR or ESRD) at 10, 20 and 30 years were 80%, 53% and 25%, while survival from ESRD were 87%, 73% and 65%, respectively. In the univariate analysis, time-average proteinuria (hazard ratio (HR) = 2.41, 95% CI 1.77-3.30), eGFR <45ml/min/1.73m2 at biopsy (HR = 2.35, 95% CI 1.03-5.32), hypertension (HR = 2.81, 95% CI 1.16-6.80), mean arterial pressure (HR = 1.02, 95% CI 1.01-1.04), tubular atrophy/interstitial fibrosis score (HR = 3.77, 95% CI 1.84-7.73), and cellular/fibrocellular crescent score (HR = 2.44, 95% CI 1.19-5.00) were found to be significant. Whereas only time-average proteinuria (TA-proteinuria) remained as a significant predictor in the multivariate analysis (HR = 2.23, 95% CI 1.57-3.16). CONCLUSION: In our cohort, TA-proteinuria was the most important predictor in the progression of IgAN, irrespective of degree of proteinuria at presentation.

Predictors of SLE relapse in pregnancy and post-partum among multi-ethnic patients in Malaysia.

Flare of Systemic Lupus Erythematosus (SLE) may occur during pregnancy and puerperium. We studied the prevalence and factors associated with SLE relapse during pregnancy and post-partum period in a multi-ethnic SLE cohort. Consecutive SLE patients who attended the outpatient clinic were reviewed for previous history of pregnancies in our institution. Patients who had a complete antenatal, delivery, and post-partum follow up were included. Their medical records were retrospectively analysed to assess the disease activity at pre-pregnancy/conception, during antenatal, and post-partum period. Presence of flare episodes during pregnancy and puerperium were recorded. The pregnancy outcomes recorded include live birth, foetal loss, prematurity and intra-uterine growth restrictions (IUGR). Univariate and multivariable logistic regression with generalized estimating equations (GEE) analyses were performed to determine the factors associated with disease relapse and the pregnancy outcomes. A total of 120 patients with 196 pregnancies were included, with a live birth rate of 78.6%. Four (2.0%) were diagnosed to have SLE during pregnancy. The flare rate in pregnancy was 40.1% while post-partum 17.4%. Majority of the relapse in pregnancy occurred in haematological system (62.3%) followed by renal (53.2%), musculoskeletal (22.1%), and mucocutaneous (14.3%). In GEE analyses, active disease at conception was the independent predictor of SLE relapse during and after pregnancy, whereas older maternal age and Malay ethnicity were associated with higher flare during post-partum. HCQ use was significantly associated with reduced risk of flare in univariate analysis but it was no longer significant in the GEE analyses. Presence of disease flare in pregnancy was significantly associated with prematurity. In conclusion, pregnancy in SLE need to be planned during quiescent state as pre-pregnant active disease was associated with disease relapse in both during and after pregnancy. Malay patients had an increased risk of post-partum flare but further larger prospective studies are needed to confirm the association between pregnancies in the different ancestral background.

Pregnancy outcomes in systemic lupus erythematosus (SLE) women.

Background Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory condition with multi-organ involvement predominantly affecting young women. There are very limited studies in pregnancy in Asian SLE patients and therefore we embarked on this study to identify pregnancy outcomes of Malaysian women with SLE. Materials and methods We performed a retrospective study of pregnancy outcomes in SLE patients in our institution from January 2007 to December 2014. A total of 71 pregnancies from 44 women were analysed. Results The mean age of our cohort was 30.5 ± 3.9 years. The rate of active disease at conception, antiphospholipid syndrome and lupus nephritis were 22.5%, 32.4% and 57.7% respectively. SLE flare occurred in 33 out of 71 pregnancies whereas 19 pregnancies were complicated with preeclampsia. The livebirth rate for our cohort was 78.9%, whilst preterm delivery was 42.9%. On univariate analysis, active disease and flare in pregnancy were both strongly associated with foetal loss and preterm delivery. Lupus nephritis (p = 0.011), SLE flare (p = 0.008) and antiphospholipid syndrome (p = 0.032) significantly increased the risk of preeclampsia. Aspirin and hydroxychloroquine were protective against foetal loss [odds ratio (OR) 0.12] and preeclampsia (OR 0.25), respectively. On multivariate analysis, active disease was a predictor of SLE flare (p = 0.002) and foetal loss (p = 0.018) and SLE flare was the main predictor of preterm delivery (p = 0.006). Conclusions Pregnancies in women with SLE should be planned and aspirin and HCQ use were beneficial in reducing adverse pregnancy outcomes.

Role of febuxostat in retarding progression of diabetic kidney disease with asymptomatic hyperuricemia: A 6-months open-label, randomized controlled trial.

Introduction: Hyperuricemia is associated with chronic kidney disease (CKD) progression and poor cardiovascular outcomes. We studied the effect of febuxostat on estimated glomerular filtration rate (eGFR), proteinuria and monitored the safety profile of the medication. Material and Methods: This is a prospective open-label, randomized study in CKD stage 3 and 4 patients with diabetic nephropathy and asymptomatic hyperuricemia. Patients were randomized into febuxostat 40 mg daily and no treatment group using block randomization method and were followed up for 6 months. Their usual care for diabetes mellitus, hypertension and dyslipidemia were continued in the study. Blood and urine investigations were monitored at baseline, 3 months and 6 months. Results: The eGFR in febuxostat group was stabilized at 6 months with no significant reduction [26.2 (IQR 14.30) at baseline to 26.3 (IQR 15.2) ml/min/1.73 m2]. Whereas, there was a significant reduction of the eGFR in no treatment group from 28.2 (IQR 17.9) to 27.6 (IQR 19.3) ml/min/1.73 m2 (p value < 0.01). We found the HbA1c (glycosylated hemoglobin) was significantly increased in febuxostat group from 7.2 ± 0.5 % at baseline to 7.6 ± 1.4 at 6 months (p value 0.04) but no significant change of HbA1c in the no treatment group. Proteinuria level was unchanged in both groups. The commonest adverse event was joint pain. Conclusions: Febuxostat was able to preserve eGFR in CKD patients with diabetic nephropathy and this effect was beyond glycemic control. Increment of HbA1c level in febuxostat group needs further larger trials.

Coupled Plasma Filtration and Adsorption (CPFA): A Single Center Experience.

BACKGROUND: Coupled plasma filtration adsorption (CPFA) is a novel extracorporeal blood purification therapy for sepsis which adsorbs both proinflammatory and anti-inflammatory mediators from filtered plasma, thereby achieving early haemodynamic stability and a reduction in inotropic support requirement. OBJECTIVES: The main objective was to review our centers' experience with CPFA in septic patients. PATIENTS AND METHODS: A retrospective chart review of all septic patients who received CPFA was performed. All patients were initially treated according to the 'surviving sepsis care bundle' with fluid resuscitation, antibiotics, and inotropes as required. CPFA was started as soon as possible after a nephrologists' assessment. RESULTS: Twenty five patients with sepsis received CPFA (15 M, 10 F, mean age 49.60 ± 18.97 years). Comorbidities included hypertension (n = 10, 40%), diabetes mellitus (n = 6, 24%), ischemic heart disease (n = 6, 24%), and an immunosuppressed state (n = 10, 40%). All patients received one cycle of CPFA with median duration of 5 (1-10) hours. CPFA was well tolerated but we encountered technical problems, especially filter clotting as CPFA was performed heparin free. 14 (56%) patients died within 28 days of treatment. CRP correlated with PCT (P = 0.040) and had an inverse trend with albumin (P = 0.066). Serum albumin was a strong predictor of mortality. CONCLUSIONS: The high prevalence of fungaemia and mortality could be attributed to many patients on chronic immunosuppressive therapy. Nonetheless, CPFA albeit expensive, does add to our armamentarium of extracorporeal treatment for severe sepsis. Regional citrate anticoagulation with CPFA may overcome problems with filter clotting.