Jason Chon Jun Choo

Severe gastrointestinal cytomegalovirus disease in two patients with renal vasculitis after immunosuppression.

Although the use of current immunosuppressive regimens has significantly improved the outcomes of autoimmune renal diseases, infectious complications remain an important clinical concern. Cytomegalovirus (CMV) infection has been shown to be one of the major causes of mortality in this group of patients. We report two cases of renal vasculitis (Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA)) that developed into severe gastrointestinal CMV disease and manifested with massive small bowel bleeding, resulting in an eventual fatal outcome for one of the patients. Risk factors, pathogenesis, role of immunosuppression in the development of CMV infection, and antiviral treatment are discussed in this review. These cases highlight the need for further research to evaluate the complex mechanisms between immunosuppression and CMV occurrence as well as the role of antiviral prophylaxis in high-risk patients undergoing immunosuppressive therapies.
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Long-Term Risk of Progressive Chronic Kidney Disease in Patients with Severe Acute Kidney Injury Requiring Dialysis after Coronary Artery Bypass Surgery

Aim: Few studies have evaluated patients after cardiac surgery for subsequent chronic kidney disease (CKD) which increases cardiovascular morbidity and mortality. This study aimed to ascertain the long-term renal outcome in adult patients with severe acute kidney injury (AKI) after coronary artery bypass graft (CABG) surgery. Methods: This is a single-center retrospective cohort study of consecutive adult patients who received acute dialysis for AKI after CABG between February 8, 2009 and January 30, 2011. Data on pre- and intra-operative factors were retrieved from electronic medical records. The primary endpoint was CKD progression as defined by dialysis dependence or doubling of serum creatinine from the pre-operative level. Secondary endpoints included in-hospital mortality and renal function at 3 months and 1 year. Results: Fifty-five patients required acute dialysis after CABG. The median age was 67 years (IQR: 61, 75), and 70.9% were male. Median pre-operative serum creatinine was 157 µmol/l (IQR: 122, 203). A total of 19 patients (34.5%) died. The median follow-up time for hospital survivors was 44.2 months (IQR: 25.0, 49.4) after surgery. Among the 36 survivors, 14 patients (38.9%) reached the primary endpoint. Patients with CKD progression had higher pre-operative serum creatinine [median 214 µmol/l (IQR: 159, 399) vs. 155 µmol/l (112, 187), p = 0.015] and lower eGFR [median 20.4 ml/min/1.73 m2 (IQR: 11.9, 38.2) vs. 39.9 ml/min/1.73 m2 (25.9, 55.5), p = 0.027] compared to those who did not have CKD progression. Conclusion: Patients with severe AKI after CABG are at high risk of long-term renal dysfunction and should be monitored regularly for deterioration.

The Singapore General Hospital Peritoneal Dialysis Programme from 2000–2008

Introduction: There is lack of data regarding outcomes of peritoneal dialysis (PD) in Singapore. The aim of this study is to retrospectively evaluate the patient characteristics, technique survival, and patient survival in a single centre. Methods: The retrospective review included 1,015 adults (47.3% female, 72.6% Chinese, mean age 58±12.4 years, mean follow-up 39.7±27.7 months) initiated on PD at the Singapore General Hospital from January 2000 to December 2008. Baseline characteristics, including cause of end-stage renal disease (ESRD), comorbid conditions, and endpoints (ie. death, transfer to HD or transplantation, renal recovery or until last follow-up on 31 December 2010) were collected. Demographic variables and patient and technique survival rates were analysed. Results: The main causes of ESRD were diabetes mellitus (DM) (58.0%), glomerulonephritis (GN) (23.3%) and hypertension (15.4%). The 1, 2, 5 and 10-year patient survival rates were 88.7%, 77.7%, 39.8% and 15.4%, respectively. Causes of death were related to infection (43.1%) and cardiac (37.8%). Patient survival rates were significantly better in PD patients with ESRD due to GN, compared with DM (5-year survival rates of 70.2% versus 22.3%, P <0.001). Patients aged 65 years and older had lower survival rates compared with those aged less than 65 years (P <0.001). The 1, 2, 5 and 10-year technique survival rates were 92.9%, 85.0%, 64.8% and 32.9%, respectively. Peritonitis was the main cause of technique failure (63.5%), and caused 13.8% of deaths. Technique survival rates were better in patients with ESRD due to GN, compared with DM (5-year survival rates of 70.9% versus 62.0%, P <0.05). Conclusion: In our single-centre retrospective review, technique survival was comparable to other East Asian centres. The poorer patient survival observed in this study may be due to older age and higher comorbidity.

Serum uric acid and AKI: is it time?

Acute kidney injury (AKI) is a well-recognized complication in hospitalized patients, with associated mortality and morbidity. Studies that aim to prevent or reverse AKI using pharmacological and interventional therapies in clinical practice have been disappointing. Work is continuing to identify potentially modifiable risk factors for AKI. Early identification and modification of these risk factors may help prevent or favorably influence the outcome of AKI. The role of uric acid as a potential risk factor is being revisited in chronic kidney disease and AKI. Apart from the established crystal precipitation with profound hyperuricemia, various non-crystal mechanisms have also been proposed in the pathogenesis of AKI. The association of serum uric acid levels with the development of AKI has been reported in various clinical settings. Together, the results of these studies highlight hyperuricemia as a potential risk factor of AKI and the need for further work on this subject.

Regional evidence and international recommendations to guide lipid management in Asian patients with type 2 diabetes with special reference to renal dysfunction

The anticipated increase in the prevalence and incidence of type 2 diabetes in Asia, and its associated cardiovascular–renal complications, will place a significant burden on patients, caregivers, and society. Despite the proven effectiveness of lipid management in reducing these complications, there are major treatment gaps, especially in Asian patients with young‐onset diabetes and chronic kidney disease (CKD). Recent international guidelines recommended the adoption of absolute risk estimation of atherosclerosis and cardiovascular disease to guide treatment intensity. These recommendations replaced the previous strategy of using low‐density lipoprotein cholesterol targets to guide initiation and intensification of lipid lowering, albeit still widely practiced in Asia. The latest guidelines also highlight the high risk of atherosclerosis and cardiovascular disease (ASCVD) for people with diabetes, who should be protected with statins, except for young patients without other risk factors, who will need yearly monitoring of blood lipid levels. Given the propensity of Asian patients with diabetes to develop CKD and the amplifying effect of CKD on ASCVD, the use of statins in Asian patients is particularly important. Due to interethnic differences in drug metabolism, rosuvastatin, which is largely cleared by the kidney, should be prescribed in low dosages (5–10 mg daily) in Asian populations. Conversely, epidemiological and experimental data confirm pleotropic and organ‐protective effects of atorvastatin, with proven safety in Asian populations within a daily dose range of 10–40 mg. Thus, there is a need for Asian countries to review and align their lipid‐lowering treatment guidelines to reduce the substantial burden of diabetes in the Asian region.

Statin-centric versus low-density lipoprotein-centric approach for atherosclerotic cardiovascular disease prevention: a Singapore perspective

The link between cholesterol levels and atherosclerotic cardiovascular disease (ASCVD) is well-established. In Singapore, there is an increasing prevalence of risk factors for ASCVD. Like many Asian countries, Singapores population is rapidly ageing and increasingly sedentary, which predisposes individuals to chronic health problems. Current international and local guidelines recommend statin therapy for the primary and secondary prevention of ASCVD. However, despite the effectiveness of statin therapy, some studies have highlighted that Asian patients with cardiovascular disease are not achieving target lipid goals. Furthermore, it is widely believed that the responses of Asians (both patients and physicians) to statin therapy are different from those of their Western counterparts. Experts convened in 2014 to determine the impact of current guidelines on clinical practice in Singapore. This review summarises the key findings and recommendations of these guidelines, and presents key principles to aid clinicians to manage the cardiovascular risk of their patients more effectively.

Asymptomatic proteinuria, renal cysts and dorsal pancreas agenesis

A 28-year-old woman was referred to our institution for evaluation of asymptomatic proteinuria. She had no significant past medical history and no family history of diabetes mellitus or kidney disease. Physical examination was unremarkable: blood pressure was 108/70 mmHg and she had no edema. Laboratory investigations found serum creatinine 74 μmol/L and normal electrolyte levels. Serum albumin was 38 g/L and liver enzymes were normal. Fasting glucose was 5.7 mmol/L. Serum complements were normal. Anti-nuclear antibody and anti-doublestranded deoxyribonucleic acid antibody were negative. Urine protein-creatinine ratio was 0.51 g/g. Urine examination under high-power field microscopy found three white blood cells and no red cells. Kidney ultrasonography found normal sized kidneys with simple subcentimeter subcortical cysts bilaterally. A computer tomography urogram found mild cortical scarring in the upper pole of the right kidney but no hydronephrosis. The urinary bladder was unremarkable. Incidentally, most of the body and tail of the pancreas was not visualized although the head and uncinate process appeared normal (Figure 1). The uterine endometrial cavity appeared to diverge at the fundus, suggesting an arcuate uterus. What is the diagnosis?

Long-term renal outcomes in multi-ethnic Southeast Asians with lupus nephritis: a retrospective cohort study: Progressive CKD in lupus nephritis

Renal involvement is common among Asians with systemic lupus erythematosus and long‐term renal outcomes have been described in homogeneous Caucasian and East Asian populations with lupus nephritis, but data are scarce for other ethnicities.

Infection mitigation a necessity in lupus patients

There are higher infection-related mortalities in Asian systemic lupus erythematosus (SLE) patients as compared to cardiovascular complications and malignancies seen in the Caucasian population [1]. However, literature evaluating infection characteristics and outcomes in Asian SLE patients is limited; hence, we read with great interest Teh et al.’s paper which highlights the significant morbidity of infections in this cohort [2]. We previously published a retrospective study evaluating the characteristics and outcomes of hospitalized lupus nephritis (LN) patients with infections [3]. In comparison to the author’s paper which involved SLE patients (64.8% had renal involvement), we found more deaths and infections among LN as compared to SLE patients which were consistent with findings from previous studies [4, 5]. There were 21 deaths (11.2%) in the author’s cohort of 125 SLE patients with infections, with a higher proportion of LN among those with infection-related deaths (80.9% vs 63.5%). We had 11 deaths (23.9%) in 46 LN patients with infection-related hospital admissions and 6 deaths (13%) were infection-related. The infection episode rate was 40.9 per 100 patient years in our LN cohort which was higher compared to 26.3 infections per 100 patient years in the author’s paper. In both studies, pulmonary infection was the most common infection and gram negative bacteria were more commonly identified with Pseudomonas being the most common gram negative organism in our study versus salmonella in Teh et al. Interestingly, cytomegalovirus (CMV) was the most commonly identified virus in our study as compared to herpes zoster in the author’s paper. The differences in characteristics of infections in our cohort likely reflect the differences in immunosuppressive therapy that LN patients were exposed to as compared to SLE patients. In our study, 37% of patients received pulsed methylprednisolone as compared to 15.5% in the author’s study. In addition, 26.1% of the patients received cyclophosphamide while only 10.7% of patients in the author’s cohort were exposed to cyclophosphamide. There were also 15.2% of patients who received Rituximab in our cohort while Rituximab use was not mentioned in Teh et al.’s paper. Other than differences in immunosuppressive regimen, differing socioeconomic factors and ethnicity composition could also account for the differences in infection characteristics in these two papers. In addition, chronic kidney disease in LN patients also confers an immuno-deficient state [6], increasing susceptibility to infections as compared to SLE patients, contributing to higher infection rates in our paper. Steroid minimization regimens with rigid steroid taper targeting doses as low as 2.5 mg by 12 weeks in the AURA trial or low dose steroid regimen (0.5 mg/kg) in MYLUPUS can reduce steroid exposure and minimize infection risk [7]. Currently, biologics such as Rituximab have also been used in steroid avoidance protocols in addition to treatment of refractory disease [8]. Furthermore, patient education with emphasis toward hand hygiene, exercising precautionary measures during travel, avoidance of ill contacts, and vigilance toward development of infective symptoms can help reduce infections. Screening for latent infections such as tuberculosis in endemic areas and timely vaccinations can also mitigate infection risk [9]. As pulmonary infections are the most common infection in SLE patients, studies evaluating the role of influenza and pneumococcal vaccination in reducing infection-related hospital admissions should be performed. There should also be consideration for CMV prophylaxis or surveillance given its high incidence in LN and other glomerulonephritis treated with potent immunosuppressant [10]. Besides, prescription of hydroxychloroquine can prevent infections in lupus patients via immunomodulatory effects [9]. In conclusion, our studies have highlighted the significant morbidity of * Peiyun Liu liu.peiyun@singhealth.com.sg

Letter to the Editor: Time for cost-effectiveness studies for preventive strategies applied according to risk of cytomegalovirus-related morbidity and mortality in ANCA-associated vasculitis

Gastrointestinal cytomegalovirus (CMV) disease in ANCA-associated vasculitis is associated with significant morbidity. Studies should be performed to identify the epidemiology and risk factors for CMV disease in AAV so that vulnerable patients may be risk-stratified for consideration of preventive strategies such as surveillance and pre-emptive therapy or anti-viral prophylaxis. Given the absence of evidence-based guidelines for prevention of CMV disease in patients with AAV receiving potent immunosuppressive therapy, further risk-benefit studies are required to ascertain if preventive strategies will reduce CMV-related morbidity and mortality in individuals with AAV.