Post transplant lymphoproliferative disorder

Introduction: Post-transplant lymphoproliferative disorder (PTLD) is a recognized complication exclusive to solid organ transplant recipients and carries a high mortality. Methods: We retrospectively reviewed records of all renal transplant recipients under follow up at our institution over the last seven years (2005-2011). We reviewed the patient characteristics, immunosuppression regimen and risk factors for the development of PTLD and its outcomes in our transplant cohort. Results: Four out of 63 patients were diagnosed with PTLD. PTLD was incidentally diagnosed on a transplant biopsy that was performed for an unexplained rise in serum creatinine in three patients. The fourth patient presented with left submandibular lymphadenopathy. Majority presented within 18 months of renal transplantation. After the diagnosis of PTLD on graft biopsy, all patients were fully investigated and two patients had systemic involvement. In the patients with systemic involvement, reduction of immunosuppression and anti B cell therapy with Rituximab was used with good success. The patient with submandibular lymphadenopathy received chemotherapy in addition to reduction of immunosuppression. Three PTLD cases were polyclonal and diagnosed early whereas the fourth case was monoclonal. Conclusion: PTLD can sometimes be incidentally diagnosed on an allograft biopsy performed for rejection. The incidence of PTLD in our centre is higher than reports from other centres but our outcome is good if recognised and treated early

Coupled plasma filtration adsorption (CPFA) plus continuous veno-venous haemofiltration (CVVH) versus CVVH alone as an adjunctive therapy in the treatment of sepsis

To compare the efficacy of Coupled Plasma Filtration and Adsorption (CPFA) plus Continuous Veno-Venous Haemofiltration (CVVH) versus CVVH alone as an adjunct treatment of sepsis in terms of haemodynamic stability, inotropic requirement and inflammatory mediators. Design and Methods: Prospective randomized controlled trial involving septic patients with/without acute kidney injury (AKI) whom were randomized to receive CPFA + CVVH or CVVH alone. Haemodynamic parameters including inotropic requirements and inflammatory mediators [procalcitonin (PCT) and C reactive protein (CRP)] were measured. Results: Twenty-three patients [CPFA + CVVH (n = 11), CVVH (n = 12)] were enrolled. Haemodynamic stability occurred earlier and sustained in the CPFA + CVVH group with an increase in diastolic blood pressure (p = 0.001 vs. p = 0.226) and mean arterial pressure (p = 0.001 vs. p = 0.575) at the end of treatment with no increment in inotropic requirement. Both groups had a reduction in PCT and CRP (CPFA + CVVH: p = 0.003, p = 0.026 and CVVH: p = 0.008, p = 0.071 respectively). The length of intensive care unit stay, hospital stay and 30 day outcomes were similar between the groups. There was an inverse association between serum albumin and CRP (p = 0.018). Serum albumin positively correlated with systolic blood pressure (p = 0.012) and diastolic blood pressure (p = 0.009). We found a trend between CRP and length of hospital stay (p = 0.056). Patients with a lower PCT at 24 h had a better outcome (survival) than those with a higher PCT (p = 0.045). Conclusion: CPFA is a feasible, albeit expensive adjunctive extracorporeal treatment that may be superior to CVVH alone in the treatment of severe sepsis

Blood pressure profile in contiuous ambulatory peritoneal dialysis patients

Background: Cardiovascular mortality is the leading cause of death in end stage renal disease. Despite being on continuous ambulatory peritoneal dialysis (CAPD), blood pressure (BP) remains poorly controlled. A higher pulse pressure and non dipping are associated with increased cardiovascular mortality. We studied BP control and the prevalence of non dipping in CAPD patients. Methods: All patients undergoing CAPD at our institution who met the inclusion criteria were recruited. We compared BP control and dipping status in diabetic and non diabetic pa-tients on CAPD. We also determined whether BP and peritoneal membrane permeability were associated. Results: Forty six patients with a mean age 45 ± 13 years were enrolled. Diabetic patients were older (mean age 54 ± 13 vs. 40 ± 11 yrs, p <0.001), had a lower mean diastolic BP (80 ± 14 vs. 90 ± 14 mmHg, p = 0.025) and a higher mean pulse pressure (59 ± 17 vs. 49 ± 14 mmHg, p = 0.035). They were also non dippers (n = 15 vs. n = 1, p = 0.007). The low and low average transporters tended to have a higher systolic BP (p = 0.054) and a higher pulse pressure (p = 0.058). On multivariate analysis, age was the main predictor of pulse pressure. Conclusion: Despite being on chronic maintenance PD, BP was not well controlled. Diabetic patients had a higher pulse pressure and were non dippers thereby increasing their cardiovascular risk. We should therefore optimize BP control and aim to restore the nocturnal dip in these patients

Regulatory T cells (CD4+CD25+FOXP3+) in lupus nephritis

Background: Systemic lupus erythromatosus (SLE) is an autoimmune disease with 20–65% of patients developing lupus nephritis (LN). Studies have reported 10% of LN patients will end up with end stage renal disease and their mortality rate is higher compared to patients without LN. Abnormality of regulatory T cells (Tregs) level is thought to be a potential factor for this LN development. The aim of study was to evaluate the percentage of Tregs in LN patients.Methods: This was a comparative cross sectional study involving LN patients and age and gender matched controls with a 2:1 ratio. The patients were grouped into active and inactive LN based on their lupus activity index; complement levels, ANA, dsDNA antibodies, ESR, SLE Disease Activity Index (SLEDAI2K) score and also urine PCI (uPCI>0.05 for active group). Disease history, demographic data, routine blood test, peripheral blood for differentials count were taken and recorded. Peripheral blood mononuclear cells were stained with CD4, CD25 and Foxp3 antibodies and percentage of Tregs was analysed using BD fluorescence-activated cell sorting (FACS) cytometer. We compared demographic and laboratory parameters between healthy controls and LN patients as well as active and inactive LN patients.Results: A total of 34 LN patients (32 females, 2 males) were recruited. Their mean age and disease duration were 37.97±11.14 years and 110.95±65.07 months respectively.  Thirteen matched controls with mean age 35.23±7.89 years were enrolled. There was no demographic difference between 2 groups of LN patients. Tregs were significantly lower in active LN compared to inactive LN and healthy control (0.44±0.37% vs. 1.89±0.46% vs. 3.12±0.56% of the CD4+, P<0.001). C3 and C4 complement fragments were significantly reduced in patients with active disease (C3; 50.92±28.43 vs. 76.31±25.63, P=0.011) and (C4; 11.17±8.41 vs. 16.70±6.50 P=0.044). Proteinuria was significantly higher while serum albumin levels were significantly lower in active patients compared to inactive patients and healthy control (urine PCI; 0.25(0.15-0.3) vs. 0.03(0.01-0.05) vs. 0.01, P<0.001) and (albumin; 29.89±6.87 vs. 36.87±3.58 vs. 40.62±1.89mmol/L, P<0.001). We found positive inversely correlation between Tregs with SLEDAI2K (r = -0.572, P=0.011) and proteinuria (r = -0.451, P=0.007).Conclusions: Tregs, C3 and C4 complements, and albumin were significantly lower while proteinuria was significantly higher in active LN. There was positive inversely correlation between the percentage of Tregs with SLEDAI2K score and proteinuria

Intravenous Rituximab in Severe Refractory Primary Focal Segmental Glomerulosclerosis

Managing primary or even secondary glomerulonephritis remains a challenge to many nephrologists. In primary focal segmental glomerulosclerosis (FSGS) with heavy proteinuria, renin aldosterone system blockade and high dose of oral prednisolone is the mainstay of treatment. Other immunosuppressive medications like Cyclophosphamide, Cyclosporine A and Mycophenolate Mofetil (MMF) are warranted if a complete remission is not achieved. We illustrate a case of 21 year old gentleman with primary FSGS that was difficult to achieve remission despite on high dose steroid and oral Cyclophosphamide. He was also not responsive to a combination of MMF and Cyclosporine A (CSA) and even throughout the therapy he developed significant steroid and CSA toxicity. He presented to our center with severe nephrotic syndrome and acute kidney injury requiring acute haemodialysis. Despite re-challenged him again on high dose prednisolone, total of 2.4g of intravenous Cyclophosphamide, and MMF, he failed to achieve remission. He was subsequently given intravenous Rituximab 500mg/weekly for 4 doses and able to attained remission for 1 year. He relapsed again and a second course of Rituximab 500mg/weekly for 6 doses were given to attain remission. This case demonstrates the difficulty in managing refractory steroid dependent FSGS and we found that Rituximab is proven beneficial in this case to induce remission

Role of febuxostat in retarding progression of diabetic kidney disease with asymptomatic hyperuricemia

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

Evaluating cardiovascular risk in chronic kidney disease patients: a biomarker approach

Cardiovascular disease (CVD) is a major cause of morbidity and mortality in chronic kidney disease (CKD) patients. This study aimed to determine the roles of CVD biomarkers in CKD patients. This was a case-control study which recruited consecutive patients with stage 2-4 CKD patients with and without CVD. Serum levels of highly-sensitive C reactive protein (hs-CRP), cystatin C (CysC), asymmetrical dimetylarginine (ADMA) and symmetrical dimethylarginine (SDMA) were measured. Sixty two stage 2-4 CKD patients with a mean age of 60.3 ± 10.4 years were recruited. Twenty three (37.1%) of them had CVD. Those CKD patients with CVD were older (64.1±8.0 vs 58.1± 1.1, p0.05). There were no differences in their mean serum levels of hs-CRP, CysC, ADMA and SDMA. Risk factors including age, diabetes mellitus, hypertension and renal functions were still the most important CVD risk factors in CKD patients

Thrombotic Thrombocytopenic Purpura in Dengue Fever

Thrombotic thrombocytopenic purpura is a rare but life threatening medical condition. Early recognition and treatment of thrombotic thrombocytopenic purpura is important especially in patients who do not present with the classic pentad to reduce the high mortality. Herein, we describe a case of a patient who does not fulfil the classic pentad features thrombotic thrombocytopenic purpura that was induced by dengue fever. The patients’ initial full blood picture did not have all the typical features of microangiopathic haemolytic anaemia but there were fragmented red blood cells. However, even a small number of fragmented red blood cells in the peripheral blood should alert physicians of the possible diagnosis of thrombotic thrombocytopenic purpura together with other symptoms. Furthermore, signs and symptoms of thrombotic thrombocytopenic purpura and dengue fever can overlap such as fever, thrombocytopenia, neurological deficit mimicking dengue encephalopathy and dengue induced acute kidney injury

Carotid intima-media thickness in kidney transplant recipients

Background/Purpose: Cardiovascular disease is the leading cause of mortality among kidney transplant recipients. Carotid intima-media thickness (CIMT) of the common carotid artery is a surrogate marker for early atherosclerosis. We wanted to compare the prevalence of increased CIMT among kidney transplant recipients with matched controls and its association with clinical and laboratory parameters. Methods: A comparative cross-sectional study involving kidney transplant recipients and controls matched for age, sex, chronic kidney disease staging, and cardiovascular risks was used. CIMT measurements were done using carotid ultrasound and considered increased if >75th percentile matched for age- and sex-matched normal controls. Standard laboratory investigations, high sensitivity C-reactive protein, and asymmetric diamethylarginine were analyzed. Results: Thirty-six kidney transplant recipients (25 men, 11 women) with a median age of 41 years [interquartile range (IQR), 38–52 years] and 36 matched controls with a median age of 44 years (IQR, 37–53 years) were enrolled. There were no demographic differences between the two groups. Kidney transplant recipients had a significantly increased CIMT, 0.8 mm (IQR, 0.6–0.9) compared to matched-controls 0.55 mm (IQR, 0.5–0.7, p = 0.001). Two thirds of kidney transplant recipients had increased CIMT, which was associated with a higher low density lipoprotein (LDL) (p = 0.022) and higher hemoglobin (p = 0.006). Smoking status (p = 0.058) and male sex (p = 0.073) had a trend towards significance to increased CIMT. Multiple linear stepwise regression demonstrated both age and hemoglobin were independent predictors of CIMT (p < 0.001). We found no relationship between high sensitivity C-reactive protein and asymmetric diamethylarginine with CIMT. Conclusion: CIMT among our kidney transplant recipients was significantly higher compared to controls thereby increasing their cardiovascular risk. 背景: 心血管疾病是腎臟移植接受者的主要死因,總頸動脈的內膜中膜厚度 (CIMT) 則是早期動脈粥樣硬化的替代性指標。在本研究中,我們比較了 CIMT 增厚於腎臟移植接受者與匹配對照組之間的盛行率,並調查了 CIMT 與臨床及實驗室參數之間的關聯。 方法: 這是一項橫斷式比較性研究,涉及的對象包括腎臟移植接受者、及與其匹配 (年齡、性別、慢性腎病分期及心血管風險) 的對照者。CIMT 以頸動脈超音波測量,增厚的定義為對應年齡性別匹配正常對照組之 > 75th 百分位數。其他測量項目除了標準實驗室參數外,亦包括高敏感度 C-reactive protein (hs-CRP) 及 asymmetric diamethylarginine (ADMA)。 結果: 分析對象包括 36 位年齡中位數 41 歲 (38,52) 之腎臟移植接受者 (25 男、11 女) 及 36 位年齡中位數 44 歲 (37,53) 之匹配對照者,兩組間的人口學特徵並無不同。腎臟移植接受者之 CIMT 為0.8 mm (0.6,0.9 mm),明顯高於匹配對照者之 0.55 mm (0.5,0.7 mm) (p = 0.001)。腎臟移植接受者之間,3 分之 2 呈現 CIMT 增厚的情形,較厚的 CIMT 與較高的低密度脂蛋白 (p = 0.022) 及較高的血色素 (p = 0.006) 有關。吸煙狀況 (p = 0.058) 及男性性別 (p = 0.073) 亦有傾向與 CIMT 增厚有關。多變項線性逐步迴歸分析顯示,年齡及血色素均是CIMT的獨立預測因子 (p < 0.001)。對於 CIMT 與 hs-CRP 或 ADMA 數值之間,我們並未發現明顯的關係。 結論: 在本研究的腎臟移植接受者中,CIMT 明顯高於對照組,因此具較高的心血管風險