Cynthia C. Lim

Chronic kidney disease, cardiovascular disease and mortality: A prospective cohort study in a multi-ethnic Asian population.

Background Few studies have examined the impact of chronic kidney disease (CKD) on adverse cardiovascular outcomes and deaths in Asian populations. We evaluated the associations of CKD with cardiovascular disease (CVD) and all-cause mortality in a multi-ethnic Asian population. Design Prospective cohort study of 7098 individuals who participated in two independent population-based studies involving Malay adults (n = 3148) and a multi-ethnic cohort of Chinese, Malay and Indian adults (n = 3950). Methods CKD was assessed from CKD-EPI estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Incident CVD (myocardial infarction, stroke and CVD mortality) and all-cause mortality were identified by linkage with national disease/death registries. Results Over a median follow-up of 4.3 years, 4.6% developed CVD and 6.1% died. Risks of both CVD and all-cause mortality increased with decreasing eGFR and increasing albuminuria (all p-trend <0.05). Adjusted hazard ratios (HR (95% confidence interval)) of CVD and all-cause mortality were: 1.54 (1.05–2.27) and 2.21 (1.67–2.92) comparing eGFR <45 vs ≥60; 2.81 (1.49–5.29) and 2.34 (1.28–4.28) comparing UACR ≥300 vs <30. The association between eGFR <60 and all-cause mortality was stronger among those with diabetes (p-interaction = 0.02). PAR of incident CVD was greater among those with UACR ≥300 (12.9%) and that of all-cause mortality greater among those with eGFR <45 (16.5%). Conclusions In multi-ethnic Asian adults, lower eGFR and higher albuminuria were independently associated with incident CVD and all-cause mortality. These findings extend previously reported similar associations in Western populations to Asians and emphasize the need for early detection of CKD and intervention to prevent adverse outcomes.

Elevated Serum Leptin, Adiponectin and Leptin to Adiponectin Ratio Is Associated with Chronic Kidney Disease in Asian Adults

Background Adiponectin and leptin, two of the key cytokines secreted by adipocytes, have been shown to be associated with cardiovascular disease. However, the association of these adipocytokines with chronic kidney disease (CKD) is not clear. We examined the association of serum adiponectin, leptin levels and leptin to adiponectin ratio (LAR) with CKD in a population-based sample of Asian adults. Methods We conducted a case-control study (450 CKD cases and 920 controls matched for age, sex and ethnicity) involving Chinese and Indian adults aged 40–80 years who participated in the Singapore Epidemiology of Eye Diseases Study (2007–2011). CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73m2 from serum creatinine. Serum adiponectin and leptin levels were measured using commercially available ELISA. Odds ratio of CKD associated with elevated adiponectin and leptin levels were estimated using logistic regression models adjusted for age, gender, ethnicity, education, smoking, body mass index, diabetes, blood pressure, total and HDL cholesterol. Results CKD cases had higher levels of leptin (mean [SD] 9.7 [11.5] vs.16.9 [20.2] ng/mL, p<0.0001) and adiponectin (10.4 [7.4] vs. 9.2 [4.2], p = 0.001) compared to controls. In multi-variable models, compared to those in the lowest quartile, the OR (95% confidence interval) of CKD among those in the highest quartile were: 6.46 (3.84, 10.88), 1.94 (1.32–2.85) and 2.88 (1.78–4.64) for leptin, adiponectin and LAR. Similar associations were also observed when adiponectin and leptin were analyzed as continuous variables. This positive association of serum adiponectin, leptin and LAR with CKD was consistently present in subgroups of gender, ethnicity, diabetes, hypertension and overweight status (all P-interaction >0.1). Conclusions Higher levels of serum adiponectin, leptin and LAR were positively associated with CKD independent of traditional risk factors in this Asian population.

Initiating acute dialysis at earlier Acute Kidney Injury Network stage in critically ill patients without traditional indications does not improve outcome: A prospective cohort study

Optimal timing for acute renal replacement therapy (ARRT) initiation in critically ill patients with acute kidney injury (AKI) is unclear. We aimed to evaluate outcomes in patients who initiated ARRT for traditional indications versus those who met Acute Kidney Injury Network (AKIN) criteria without traditional indications.

Severe infections in patients with lupus nephritis treated with immunosuppressants: a retrospective cohort study

Lupus nephritis (LN) is associated with significant morbidity and mortality and hence usually treated aggressively with immunosuppressants. This predisposes LN patients to increased infections, yet few studies have evaluated LN patients for infective complications. We aimed to describe the epidemiology and identify risk factors for infections requiring hospitalization among patients with biopsy‐proven LN.

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.

Epidemiology and risk factors for cytomegalovirus infection in glomerular diseases treated with immunosuppressive therapy

Cytomegalovirus (CMV) infections are associated with morbidity and mortality. We aimed to describe the epidemiology, risk factors and outcomes of CMV infection among patients with glomerulonephritis (GN) who received potent immunosuppressants (IS).

Infections in hospitalized lupus nephritis patients: characteristics, risk factors, and outcomes

Background There are limited studies documenting infection epidemiology in lupus nephritis (LN) patients. We aimed to study infection incidences and risk characteristics and ascertain possible predictors of infective outcomes in a multiethnic Asian population. Methods This retrospective study from 2006 to 2012 included newly diagnosed LN patients. We collected admissions, immunosuppression, and infection data until end-stage renal failure, death, last follow-up, or the year 2015. The infection incidence rates were evaluated and a generalized linear latent and mixed models (GLLAMM) analysis was carried out to evaluate potential predictors of infection. Results Our cohort of 101 patients consisted of mainly Chinese (75.2%), females (78.2%), and a median age of 38 years (IQR 26–49). The median time of follow-up was 72.8 months (IQR 49.5–94.0). Six out of 14 patient deaths were infection related. Seventy-eight out of 200 admissions, with a total of 102 episodes of infection, occurred in 46 patients. The incidence of infection rates leading to admissions was 10.3 per 100 person-years and the incidence of infection episodes rates was 17.6 per 100 person-years. Cytomegalovirus (CMV) was the most common organism identified. Univariate GLLAMM analysis showed Malay compared to Chinese ethnicity (HR 2.833 (95% CI 1.088–7.373)), use of oral cyclophosphamide (HR 6.618 (95% CI 1.015–43.154)) and rituximab (HR 3.967 (95% CI 1.157–13.603)) as predictors of infection-related admissions. Malay ethnicity and rituximab remained significant in the multivariate GLLAMM analysis. Conclusions Our study highlights substantial infection incidences in patients with LN and its contribution to deaths.

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?

End-stage renal disease in tuberous sclerosis complex-polycystic kidney disease contiguous gene syndrome: epidemiology, clinical manifestations and implications for transplantation.

A 31-year-old woman presented with worsening lower limb edema over 2 weeks. Five months prior, she had gross hematuria and evaluation found enlarged kidneys and azotemia, but she defaulted follow-up. She had no history of seizures nor intellectual disability. There was no family history of kidney disease. Examination found her to be hypertensive with multiple facial angiofibromas, ballotable kidneys and 3? pedal edema. Investigations showed serum creatinine 1,390 lmol/L, metabolic acidosis and anemia. Computer tomography found pulmonary lymphangioleiomyomatosis (LAM), enlarged polycystic kidneys and angiomyolipomas (AMLs), as well as liver cysts. Brain imaging revealed multiple cortical and subcortical tubers and a calcified subependymal hamartoma. Retinal photography noted bilateral retinal astrocytomas. Echocardiography was negative for cardiac rhabdomyoma. These features suggested a clinical diagnosis of tuberous sclerosis. Genetic testing with array comparative genomic hybridization found a 10-kilobase deletion at chromosome 16p13.3 from chr16: 2,136,809–2,146,877 (hg19). The deleted region encompassed the terminal exons of the TSC2 and PKD1 genes. This was confirmed by quantitative real-time polymerase chain reaction. The patient was commenced on regular hemodialysis for end-stage renal disease (ESRD) with plans for bilateral nephrectomy and subsequent kidney transplant. Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited genetic disorder caused by mutations of either TSC1 on chromosome 9 or TSC2 on chromosome 16 which encode for hamartin and tuberin, respectively. Abnormalities in these proteins result in characteristic hamartomas in multiple organs. Diagnosis is based on clinical and radiological criteria [1]. Renal involvement in TSC includes AMLs in 40–80 % and cysts in 30–50 %, but ESRD was uncommon [2, 3]. The PKD1 gene lies adjacent to TSC2 locus on chromosome 16. Large PKD1 deletions involving the adjacent TSC2 gene was termed TSC2/PKD1 contiguous gene syndrome (CGS). It is found in 2–3 % of patients with TSC and causes early onset polycystic kidney disease and renal impairment [4, 5]. A series of 17 TSC2/ PKD1 CGS cases found that all had polycystic kidneys in childhood; renal function deteriorated in adolescence and three developed ESRD at ages 19, 20 and 29 years [5]. Given that ESRD occurs in young adulthood in TSC2/ PKD1 CGS, renal transplantation may be the preferred renal replacement therapy. However, literature on renal transplantation in TSC2/PKD1 CGS is scarce. Thus, choice of immunosuppression and management of malignancy risk and extra-renal complications are usually extrapolated from TSC transplant recipients. Among TSC ESRD patients, mammalian target of rapamycin protein inhibitors (mTORi) as maintenance immunosuppression post-transplant resulted in good graft outcomes and improvement in extra-renal manifestations [6]. Renal cancers are common in TSC ESRD and may be increased with post-transplant immunosuppression [3]. Moreover, large AMLs are more susceptible to spontaneous bleeding. Thus, pre-emptive bilateral nephrectomy should be considered. Otherwise, C. C. Lim (&) H. Tan S. Thangaraju M. W. Y. Foo Department of Renal Medicine, Singapore General Hospital, Level 3 Academia, 1 Hospital Drive, Outram Road, Singapore 169608, Singapore e-mail: cynthia.lim.c.w@sgh.com.sg

An Introduction to Extracorporeal Blood Purification in Critical Illness

Critical care nephrology is an emerging sub-specialty with rapid technological advancement and a growing body of dedicated literature in blood purification techniques. Their applications have been extended to improve morbidity and survival in multiple organ dysfunctions. Novel techniques have also allowed us to push the frontiers in transplant medicine, giving high-immunological risk patients a chance at a kidney transplant where this was previously precluded by hyperacute antibody-mediated rejection. We aim to review the myriad extracorporeal blood purification techniques now available for treating various critical illnesses in our clinical practice. Some of these techniques will still require further clinical research to determine the optimal timing and dose in order to achieve significant improvement in clinical outcomes.