Kok-Seng Wong

Global evolutionary trend of the prevalence of primary glomerulonephritis over the past three decades.

Objective: The prevalence of primary glomerulonephritis in Singapore is compared with that of 28 other countries to review changing trends in the evolution of primary glomerulonephritis in Asia and other countries. Method: 2,586 renal biopsies in Singapore over the past 3 decades were reviewed and compared with data from 28 other countries. Results: In the 1st decade most Asian countries have mesangial proliferative glomerulonephritis as the most common form of primary glomerulonephritis, and in the 3rd decade there has been a dramatic increase in focal and segmental glomerulosclerosis reflecting aging and obesity in keeping with more developed countries. IgA nephritis remains the commonest glomerulonephritis in many countries. Membranous glomerulonephritis continues to be more prevalent in Western countries while mesangial proliferative glomerulonephritis remains prevalent in many Asian countries. Conclusion: Apart from geographical and genetic influences, socioeconomic factors may play a role in the evolution of the biopsy pattern in some countries. Worldwide, the prevalence of focal segmental glomerulosclerosis continues to increase. In third world countries some of the commoner forms of glomerulonephritis are related to infections, in contrast to developed countries where the antigenic exposure may be related to diet, allergens and other industrial agents.

Renin-Angiotensin System Gene Polymorphisms: Its Impact on IgAN and Its Progression to End-Stage Renal Failure among Chinese in Singapore

Background: Gene polymorphisms in angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II type 1 receptor (ATR) had been associated with IgA nephropathy (IgAN) and its progression. Several studies on Caucasian and Japanese had reported contradicting results. We determined these polymorphisms in 118 Chinese patients with IgAN and 94 healthy Chinese to assess their clinical impact. Methods: Genotyping was performed with DNA from peripheral leukocytes, PCR amplification of the polymorphic sequence, restriction enzymes digestion, separation and identification of DNA fragments. Clinical data at renal biopsy and final status on renal function were determined from patients’ records. Results: Among controls, genotype distributions were in Hardy-Weinberg equilibrium. Comparing all IgAN patients with controls, AGT and ATR genotype distributions were similar whereas there was significant increase in the ACE DD genotype (p < 0.05). Comparing patients with end-stage renal failure (IgAN-ESRF) and without (IgAN-nonESRF), there was no difference in any of the three gene polymorphisms. But in contrast, there were significant differences in higher male prevalence (p < 0.05), increased serum creatinine at presentation (p < 0.05), more sclerosis (p < 0.01) and higher tubulointerstitial lesion score (p < 0.001) in the IgAN-ESRF group. Conclusion: Among the ACE, AGT and ATR gene polymorphisms, only the DD genotype may predispose the individual to IgAN in our Chinese population. In contrast to clinical and histological risk factors, these genetic variations showed no impact on disease progression to ESRF. It is unlikely that genotyping more patients will prove these genes useful. Nevertheless, preclinically determined genetic markers are very useful as risk factors for disease occurrence and as prognostic indices for disease progression. Therefore, continuing efforts should be made to look at other genes to find those with significance.

Epstein–Barr virus-associated smooth muscle tumors after kidney transplantation: treatment and outcomes in a single center

Epstein–Barr virus‐associated smooth muscle tumors (EBV SMT) in adult kidney transplant recipients (KTR) are rare. The aims of this study are to document the clinical features, types of treatment given, and outcomes of KTR with EBV SMT in our institution.

Polymorphism of renin-angiotensin system genes in IgA nephropathy.

Background and Aims:  Individuals are prone to disease because of certain disease‐susceptible genes. The angiotensin I‐converting enzyme (ACE) gene insertion/deletion (I/D), the angiotensinogen (AGT) gene, M235T, and the angiotensin II type 1 receptor (ATR) gene, A1166C, polymorphisms have been associated with IgA nephropathy (IgAN) and its progression. Several studies on Caucasians and Japanese patients have reported contradictory results. We determined these polymorphisms in 118 Chinese patients with IgAN and 94 healthy Chinese subjects to assess their clinical impact.

Isoelectric focusing and selectivity index in IgA nephrotic syndrome.

Proteinuria in 13 patients with IgA nephritis with nephrotic syndrome (IgANS) was analysed by isoelectric focusing (IEF) and compared with 12 patients with minimal change nephrotic syndrome (MCNS) (n = 8) or focal global sclerosis nephrotic syndrome (FGS) (n = 4) to determine the pattern of proteinuria on IEF and to assess the value of IEF and protein selectivity index (SI) as predictors of response to therapy with predisolone or cyclophosphamide. Steroid/cyclophosphamide responsive patients with IgANS had SC:UA (cationic serum albumin with anionic urine albumin) or SA:UC (anionic serum albumin with cationic urine albumin) IEF patterns and steroid/cyclophosphamide unresponsive patients with IgANS had an SC:UC (cationic serum albumin with cationic urine albumin) IEF pattern. The majority of patients with MCNS or FGS who had an SA:UC IEF pattern were steroid responsive. SI was a better predictor of steroid/cyclophosphamide responsiveness in patients with IgANS (r = 0.78, p < 0.002 compared to IEF, r = 0.64, p < 0.02).

The contribution of chronic kidney disease to the global burden of major noncommunicable diseases

To the Editor: We have read the report of the ISN Global Outreach Programme,1 which confirms that, for the less developed countries compared with the more developed ones, chronic glomerulonephritis (GN) and not diabetic nephropathy (DiabNx) is still the leading cause of end-stage renal failure (ESRF).

Albumin dialysis in critically ill patients: use versus omission of intradialytic heparin.

Albumin liver dialysis using the Molecular Adsorbent Recirculating System (MARS) (Teraklin AG, Rostock, Germany) is used in severe acute liver failure (ALF). We hypothesized that intradialytic heparin worsens preexisting hemostatic defects without enhancing system longevity or therapeutic efficacy. This was a retrospective, single center study of 10 critically ill patients (M : F = 8:2; mean age 58.5 +/- 16.5 years old; Acute Physiology and Chronic Health Evaluation II 25.0 +/- 3.5) treated with 31 MARS sessions (intradialytically heparinized : nonheparinized = 18:13). Mortality in this cohort was 80%. All MARS circuits were primed with dilute heparinized saline before commencement. However, intradialytic, intermittent, bolus heparin was administered on an ad hoc basis with circuit saline flush where indicated. Acute renal replacement therapy was instituted where indicated. Average total intradialytic heparin used was 757 +/- 389 IU. Circuit pressures were stable with or without intradialytic heparin. Significant reductions in serum urea, creatinine, ammonia, and total bilirubin were achieved using intradialytically heparinized and nonheparinized MARS. Thrombocytopenia and elevated activated partial thromboplastin time (aPTT) were further deranged post-MARS for both circuit types, but significantly so in intradialytically heparinized MARS: pre- versus post-MARS aPTT (s) 57.8 +/- 17.6 versus 88.7 +/- 48.0, P = 0.011, and platelet count (x 10(3)/L) 102.9 +/- 61.1 versus 84.4 +/- 50.5; P = 0.009. The use of low dose, intradialytic heparin during MARS exacerbates preexisting severe coagulopathy and thrombocytopenia in patients with severe ALF without enhancing circuit function and longevity. However, the role and safety of heparinized saline prime need further investigation.

MARS therapy in critically ill patients with advanced malignancy: a clinical and technical report

Abstract  

Cyclosporin hypertension in the Wistar rat : role of uninephrectomy

1. The effects of cyclosporin A (CyA) solution (1–50 mg/kg per day), CyA powder (5–20 mg/kg per day) and vehicle, and the effects of renal mass reduction on CyA induced hypertension, were examined in conscious Wistar rats.

Impact of patterns of proteinuria on renal allograft function and survival: a prospective cohort study.

Suhail SM, Kee TSY, Woo KT, Tan HK, Yang WS, Chan CM, Foo MWY, Li HH, Siddique MM, Wong KS. Impact of patterns of proteinuria on renal allograft function and survival: a prospective cohort study.
Clin Transplant 2011: 25: E297–E303.