Human leucocyte antigens profiling in Malay female patients with systemic lupus erythematosus: are we the same or different?

OBJECTIVE: SLE is a heterogeneous autoimmune disease, in terms of clinical presentation, incidence and severity across diverse ethnic populations. We investigated the human leucocyte antigens (HLA) profile (ie, HLA-A, HLA-B and HLA-C, HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-DPA1 and HLA-DPB1) in Malaysian Malay female patients with SLE and determined the generalisability of the published HLA risk factors across different ethnic populations globally including Malaysia. METHODS: One hundred Malay female patients with SLE were recruited between January 2016 and October 2017 from a nephrology clinic. All patients were genotyped for HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-DPA1 and HLA-DPB1 alleles using PCR sequence-specific oligonucleotides method on Luminex platform. A total of 951 HLA genotyped population-based Malay control subjects was used for association testing by means of OR with 95% CIs. RESULTS: Our findings convincingly validated common associations between HLA-A*11 (OR=1.65, p=3.36×10-3, corrected P (Pc)=4.03×10-2) and DQB1*05:01 (OR=1.56, p=2.02×10-2, Pc=non-significant) and SLE susceptibility in the Malay population. In contrast, DQB1*03:01 (OR=0.51, p=4.06×10-4, Pc=6.50×10-3) were associated with decreased risk of SLE in Malay population. Additionally, we also detected novel associations of susceptibility HLA genes (ie, HLA-B*38:02, DPA1*02:02, DPB1*14:01) and protective HLA genes (ie, DPA1*01:03). When comparing the current data with data from previously published studies from Caucasian, African and Asian populations, DRB1*15 alleles, DQB1*03:01 and DQA1*01:02 were corroborated as universal susceptibility and protective genes. CONCLUSIONS: This study reveals multiple HLA alleles associated with susceptibility and protection against risk of developing SLE in Malay female population with renal disorders. In addition, the published data from different ethnic populations together with our study further support the notion that the genetic effects from association with DRB1*15:01/02, DQB1*03:01 and DQA1*01:02 alleles are generalised to multiple ethnic populations of Caucasian, African and Asian descents.

Predictors of severe leptospirosis: a multicentre observational study from Central Malaysia.

BACKGROUND: Leptospirosis is a re-emerging disease with vast clinical presentations, that ranges from subclinical or mild to severe and fatal outcomes. Leptospirosis can be managed well if diagnosed earlier, however, similar clinical presentations by several other febrile illnesses or co-infections, and laboratory diagnostic challenges due to the biphasic nature of the illness, often result in mis- or underdiagnosis, thereby lead to severe illness. Identification of clinical predictors for the severe form of the disease plays a crucial role in reducing disease complication and mortality. Therefore, we aimed to determine the clinical predictors associated with severe illness among leptospirosis patients from Central Malaysia through a prospective multicenter observational study. METHODS: A prospective multicenter observational study was performed on patients admitted for clinically suspected leptospirosis. Three hospitals namely Hospital Serdang, Hospital Tengku Ampuan Rahimah and Hospital Teluk Intan were included in the study. Among a total of 165 clinically suspected leptospirosis patients, 83 confirmed cases were investigated for clinical predictors for severe illness. Qualitative variables were performed using χ2 and the relationship between mild and severe cases was evaluated using logistic regression. Multivariable logistic regression was used to predict the independent variable for severity. RESULTS: Among the 83 patients, 50 showed mild disease and 33 developed severe illness. The mean age of the patients was 41.92 ± 17.99 and most were males (n = 54, 65.06%). We identified mechanical ventilation, acute kidney injury, septic shock, creatinine level of > 1.13 mg/dL, urea > 7 mmol/L, alanine aminotransferase > 50 IU, aspartate aminotransferase > 50 IU, and platelet < 150 × 109/L as factors associated with severe illness. Acute kidney injury, alanine aminotransferase > 50 IU and platelet < 150 × 109/L were defined as the independent factors for severity. CONCLUSIONS: Lungs, liver and kidney involvement and septic shock were found as the prognostic factors for severe leptospirosis. Acute kidney injury, high level of alanine aminotransferase and low level of platelets were found to be independent predictors of severity.

Melanosis coli in a peritoneal dialysis patient: a case report.

BACKGROUND: Patients who undergo peritoneal dialysis (PD) are at risk of gut bacteria translocation leading to peritonitis when there is chronic diarrhea. Chronic diarrhea is defined as any course of diarrhea that lasts at least 4 weeks, which can be continuous or intermittent. Chronic diarrhea of any duration may cause dehydration, electrolyte imbalance, and life-threatening hypovolemic shock. In PD patients, excessive ultrafiltration from the exchanges, combined with severe gastrointestinal loss, may cause hypovolemic shock, electrolyte imbalance, and metabolic acidosis. There are multiple causes of chronic diarrhea in PD patients including infective causes, mitotic lesions, and rarely the regular and excessive use of laxatives, which is a diagnosis of exclusion. CASE PRESENTATION: We report a case of Melanau lady with chronic diarrhea secondary to laxative usage in a patient being treated with automated peritoneal dialysis (APD). The patient went into hypovolemic shock, but luckily did not contract peritonitis. A colonoscopy revealed brown to black discoloration of the colon, a feature suggestive of melanosis coli. A biopsy of the intestine further confirmed the diagnosis by histopathological examination. Withdrawal of laxatives and the introduction of probiotics improved the symptoms tremendously. CONCLUSIONS: The chronic use of laxatives in PD patients can potentially lead to a devastating problem; thus, the management team must monitor treatment commencement appropriately.

Blood and urine biomarkers in chronic kidney disease: An update.

INTRODUCTION: Chronic kidney disease (CKD) is a silent disease. Most CKD patients are unaware of their condition during the early stages of the disease which poses a challenge for healthcare professionals to institute treatment or start prevention. The trouble with the diagnosis of CKD is that in most parts of the world, it is still diagnosed based on measurements of serum creatinine and corresponding calculations of eGFR. There are controversies with the current staging system, especially in the methodology to diagnose and prognosticate CKD. OBJECTIVE: The aim of this review is to examine studies that focused on the different types of samples which may serve as a good and promising biomarker for early diagnosis of CKD or to detect rapidly declining renal function among CKD patient. METHOD: The review of international literature was made on paper and electronic databases Nature, PubMed, Springer Link and Science Direct. The Scopus index was used to verify the scientific relevance of the papers. Publications were selected based on the inclusion and exclusion criteria. RESULT: 63 publications were found to be compatible with the study objectives. Several biomarkers of interest with different sample types were taken for comparison. CONCLUSION: Biomarkers from urine samples yield more significant outcome as compare to biomarkers from blood samples. But, validation and confirmation with a different type of study designed on a larger population is needed. More comparison studies on different types of samples are needed to further illuminate which biomarker is the better tool for the diagnosis and prognosis of CKD.

Immune thrombocytopenic purpura masking the fatal potential of calciphylaxis in a haemodialysis patient.

Calciphylaxis on the background of immune thrombocytopenic purpura (ITP) has never been described. The pathogenesis of calciphylaxis is complex and not fully understood as yet. ITP has a complex pathogenesis that leads to bleeding or thrombotic events. Although ITP is treatable and reversible, calciphylaxis on the other hand, responds poorly to treatment and carries high mortality and morbidity. We present a case of a 56-year-old lady with end-stage renal disease with ITP, who complained of 1-month history of painful necrotic patches over the thighs. Due to delayed diagnosis, the patient deteriorated and passed away despite aggressive multidisciplinary approach. This case highlights the importance of early recognition of the increased thrombotic risk in an end-stage renal failure patient with poor phosphate control and ITP.