Kw Chan

Significance of TWIST and E-cadherin expression in the metastatic progression of prostatic cancer.

Aim:  Development of metastasis is one of the main causes of prostatic cancer‐related death. We have previously found that up‐regulation of TWIST, a highly conserved basic helix–loop–helix transcription factor, in prostatic cancer cells can promote epithelial to mesenchymal transition through down‐regulation of E‐cadherin. The present study aimed to investigate the prognostic significance of TWIST and to correlate TWIST and E‐cadherin expression in prostatic cancer specimens.

Living-Related Renal Transplantation in a Patient with Nail-Patella Syndrome

Living-related renal transplantation was performed successfully in a patient with nail-patella syndrome. Graft biopsy 18 months post-transplantation showed normal glomerular basement membrane by electron microscopy. Dystrophic nails of both index fingers had also regrown, suggesting the donor kidney might replenish deficient factors.

Immunoglobulins (IgG, IgA, IgM, IgE) and complement components (C3, C4) in nephrotic syndrome due to minimal change and other forms of glomerulonephritis, a clue for steroid therapy?

Serum IgG, IgA, IgM, IgE, C3 and C4 were measured in 13 patients with minimal change (MC) glomerulonephritis and 10 with the nephrotic syndrome (NS) due to other forms of glomerulonephritis. The tests were repeated in all patients with MC glomerulonephritis when they went into remission. Serum IgG was reduced, IgM, IgE and C3 were raised while serum IgA was within the normal range when the patients were nephrotic. Changes in serum immunoglobulins and complement components were not specific to MC glomerulonephritis and these parameters reverted towards normal when the NS went into remission. Elevated C3 levels probably reflected increased hepatic protein synthesis since C3 correlated significantly with serum cholesterol. There was a tendency for serum IgE concentrations to positively correlate with the total dose of prednisolone required to bring the NS to remission.

Focal Sclerosing Glomerulopathy Risk Factors of Progression and Optimal Mode of Treatment

Focal sclerosing glomerulopathy and especially focal segmental glomerulosclerosis (FSGS) have been recognized as a distinct clinical entity, however, there still exist controversies in terms of prognostic risk factors of progression and optimal mode of treatment. A total of 32 patients (2 with focal global sclerosis; FGS, the remainder with FSGS) were followed up for a mean period of 82 months (3–240 months). Fourteen presented with nephrotic syndrome and 18 had proteinuria with or without hypertension. Thirteen patients, all of whom except 1 were nephrotic, received steroid treatment with or without other immunosuppressive agents (cyclophosphamide/cyclosporin A/azathioprine). Three of the steroid-treated remained stable in complete remission; 5 nephrotic non-responders had renal death. The mean slope of 1/creatinine versus time for steroid-treated and non-treated groups was −0.23 and −0.043, respectively (p=0.04), suggesting that nephrotic range proteinuria might be prognostically important. However, for the population of FSGS/FGS as a whole, only the initial serum creatinine predicted renal survival (p=0.001 by Coxs regression model). Hypertension and hypercholesterolaemia were not important variables by themselves. Nevertheless, we found that the 9 patients treated with antihyperlipidaemics (gemfibrozil/probucol/cholestyramine/maxEPA) fared better, mean slope being −0.023 versus −0.103 for non-treated, though not reaching statistical significance (p=0.96). Controlled prospective study involving a larger number of patients might be worthwhile.

A randomized prospective comparison of nadolol, captopril with or without ticlopidine on disease progression in IgA nephropathy

To determine if angiotensin converting enzyme inhibitors (ACEI) and antiplatelet agents have any added advantages over beta‐blockers in preventing disease progression in IgA nephropathy (IgAN), 52 patients with IgAN with at least two features suggestive of progressive disease, namely, proteinuria >1 gm/day, mean blood pressure (MBP)>107 mmHg, serum creatinine 0.12–0.4 mmol/L and the presence of glomerulosclerosis and/or tubulointerstitial fibrosis on initial biopsy were randomized to receive nadolol (N), captopril (C) and captopril plus ticoplidine (CT). In hypertensive subjects, the dose N and C was adjusted to normalize MBP. In normotensive subjects the dose was adjusted to achieve a reduction of MBP of 5–10mmHg. Five patients withdrew prematurely before reaching the end of the study period. The results after a minimal period of 3 years follow‐up were available in the remaining 47 patients (n=16, 12 and 19 in groups N, C and CT, respectively). Target of blood pressure (BP) treatment was achieved in all patients and the post‐treatment MBP was comparable among the three groups. In C and CT, peripheral blood renin increased significantly while in CT, in vitro platelet aggregation decreased significantly following treatment. Urinary protein and albumin excretion decreased significantly in all treatment groups but there was no difference among the three groups. Progression of renal failure as measured by life table analysis of the percentage of patients with doubling of serum creatinine and by the slope of the reciprocal of serum creatinine (mean±SEM: −0.021±0.014; −0.016±0.010 and −0.017±0.008 for N, C and CT, respectively) and of glomerular filtration rate as measured by plasma disappearance of injected Cr51EDTA over time (mean±SEM: −0.556±0.157, −0.739±0.304 and −0.543±0.274 for N, C and CT) were similar among the three groups. In this small comparative study, ACEI does not appear to be better than long‐acting beta‐blocker in retarding disease progression in patients with IgAN and ticlopidine confers no additional benefit.

Identification of Bruton tyrosine kinase mutations in 12 Chinese patients with X-linked agammaglobulinaemia by long PCR-direct sequencing.

X‐linked agammaglobulinaemia (XLA) is an immunodeficiency caused by Bruton tyrosine kinase (BTK) gene mutations. The disease is characterized by recurrent bacterial infections and profound hypogammaglobulinemia with marked reduction or lack of mature B‐cells in the peripheral blood. Molecular characterization of BTK gene provides an opportunity for definitive diagnosis of XLA patients, especially for those with atypical phenotype resulting in a milder or late‐onset form of the disease. The diagnosis allows accurate carrier detection with subsequent genetic counselling and prenatal diagnosis. In this study, long polymerase chain reaction (PCR)‐direct sequencing analysis of the BTK gene in 12 unrelated Chinese XLA patients had been performed. Eight recurrent mutations and four novel mutations were identified. This is the first report of Chinese cases from three different East Asia regions together, including Hong Kong, Singapore and mainland China. Future clinical and genetic information from the undiagnosed Chinese XLA patients may provide insight into the genotype–phenotype correlations of BTK gene.

Crescentic IgA glomerulonephritis following interleukin-2 therapy for hepatocellular carcinoma of the liver

A patient who developed crescentic IgA nephropathy following treatment with recombinant interleukin-2 (rIL2) and lymphokine-activated killer (LAK) cell therapy for hepatocellular carcinoma was reported. Cessation of rIL2 and LAK cell treatment plus plasmapheresis and steroid therapy was successful in achieving partial improvement and stabilization of renal function. This is the first case report of biopsy-documented glomerulonephritis developing after IL2 and LAK cell therapy. This provides indirect in vivo evidence for the role of IL2 in mediating glomerular injury in IgA nephropathy.

Determination of mismatched donor HLA in kidney transplant recipients with unknown donor HLA phenotypes

Kwok J, Chan GSW, Lam MF, Yan T, Tang L, Kwong KM, Chan KW, Chan TM. Determination of mismatched donor HLA in kidney transplant recipients with unknown donor HLA phenotypes.
Clin Transplant 2010 DOI: 10.1111/j.1399‐0012.2010.01246.x 
© 2010 John Wiley & Sons A/S.

Burkholderia urinary tract infection after renal transplantation

Abstract: Urinary tract infection is a common complication after renal transplantation. The etiologies are diverse and the bacterial agents may sometimes be acquired during the hospital stay. We report a patient who developed Burkholderia cepacia urinary tract infection after renal transplantation. The bacteria showed in vivo resistance to all of the available antibiotics. A graft nephrectomy was eventually required to clear the infection. The consequence of some fastidious infection may be catastrophic and early recognition and treatment is necessary to optimize the treatment.

Thrombotic microangiopathy in an allograft kidney: a diagnostic challenge

Sir: Thrombotic microangiopathy (TMA) is a microvascular occlusive disorder characterized by aggregation of platelets, thrombocytopenia, fragmentation of erythrocytes, elevated serum lactate dehydrogenase and haemolytic anaemia. It is a serious complication after renal transplantation and can be predominantly renal or systemic. Haemolytic uraemic syndrome ⁄ thrombotic thrombocytopenic purpura (HUS ⁄ TTP) is the systemic manifestation of TMA. Acute vascular rejection can give similar clinical and histological features to HUS ⁄ TTP. The only lesion specific for vascular rejection appears to be endovasculitis. We report a case of TMA in a renal allograft which illustrates the diagnostic difficulty and the potential value of C4d in the differential diagnosis. A 39-year-old lady had end-stage renal failure of unknown aetiology. The first cadaveric renal transplant was performed in Guangtong, China in 1993. Steroid-resistant acute rejection developed on postoperative day 14, followed by graft nephrectomy on day 25. The detailed pathological findings could not be traced. She had a second cadaveric renal transplantation in 2003, with the latest panel reactive antibody before transplant being 0% and direct tissue crossmatch negative. Tacrolimus, prednisolone, azathioprine and basiliximab were used for prophylactic immunosuppression. Oliguria and an increasingly elevated creatinine developed from postoperative day 5 onwards. Urgent renal biopsy was done 1 and 3 weeks after transplantation. In both renal biopsy specimens, the glomeruli exhibited segmental microthrombi (Figure 1), accompanied by swelling of endothelial cells. Myointimal cell proliferation and mucoid intimal changes were also seen in the interlobular renal arteries. There was no diagnostic evidence of acute cellular rejection. No endovasculitis was observed in the interlobular and larger branches (total 1⁄4 10) of the renal artery examined. Immunofluorescence studies showed focal mild deposits of IgM only. Ultrastructural studies revealed diffuse electron-lucent widening of the lamina rare interna of the glomerular basement membrane by ‘fluffy’ material. A diagnosis of thrombotic microangiopathy was made. The patient had episodic neurological symptoms and confusion. Urgent computed tomography of the brain was unremarkable. Fragmented red blood cells were seen in a peripheral blood smear. Because there was no endovasculitis on either occasion, the features are consistent with HUS ⁄ TTP. Tacrolimus was replaced by rapamycin because of the risk of TTP. Plasmapheresis with cryosupernatant replacement and supportive haemodialysis were performed, but there was no recovery of renal function. Graft nephrectomy was subsequently performed 6 weeks after transplantation. The glomeruli exhibited similar changes to those seen in previous biopsies. Endovasculitis, characterized by mononuclear cells beneath activated endothelial cells, was apparent in the larger branches of the renal artery (Figure 2). Subsequently, immunohistochemistry using a polyclonal anti-C4d antibody was performed on formalinfixed paraffin-embedded sections. Widespread, strong and circumferential C4d staining was noted in the peritubular capillaries of the previous two needle biopsy and nephrectomy specimens, establishing a diagnosis of acute humoral rejection. The absence of endovasculitis in the initial two renal biopsy specimens was consistent with HUS ⁄ TTP. It was not until examination of the nephrectomy specimen that a component of acute vascular rejection was found. The diffuse positivity of C4d, a marker of acute humoral rejection, was also of interest. Coexistence of TMA and C4d has been reported, but Figure 1. Light microscopy of a glomerulus shows intraluminal thrombus (PAS stain). Correspondence 775