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Background: Various glomerular pathologies have been reported in patients who have undergone haematopoietic stem cell transplantation (HSCT), but the data on clinico-pathological correlations and clinical outcome remain limited. Methods: We analysed the clinical and histopathological data of patients who had biopsy-proven de novo glomerular diseases after HSCT since 1999. Results: A total of 2204 patients underwent HSCT during the period 1999-2021, and 31 patients (1.4%) developed de novo glomerular diseases after a mean duration of 2.8 ± 2.7 years after HSCT. Fifteen of these patients (48.4%) had graft-versus-host-disease prior to or concomitant with renal abnormalities. Proteinuria and eGFR at the time of kidney biopsy were 4.1 ± 5.3 g/day and 50.8 ± 25.4 mL/min/1.73 m2, respectively. Kidney histopathologic diagnoses included thrombotic microangiopathy (TMA) (38.7%), membranous nephropathy (MN) (25.8%), mesangial proliferative glomerulonephritis (12.9%), minimal change disease (9.7%), focal segmental glomerulosclerosis (9.7%) and membranoproliferative glomerulonephritis (3.2%). Immunosuppressive treatment was given to patients who presented with nephrotic-range proteinuria and/or acute kidney injury, while renin-angiotensin-aldosterone blockade was given to all patients with proteinuria ≥1 g/day, with complete and partial response rates of 54.8% and 19.4%, respectively. One patient with TMA progressed to end-stage kidney disease after 24 weeks, and two patients, one with TMA and one with MN, (6.4%) progressed to chronic kidney disease (CKD) Stage ≥3. Kidney and patient survival rates were 96.6% and 83.5%, respectively, at 5 years. Conclusion: De novo glomerular diseases with diverse histopathologic manifestations affect 1.4% of patients after HSCT, and approximately 10% develop progressive CKD.

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STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti-IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder.

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Background: The mortuary plays an important, under-recognized role in end-of-life care. A 'Life-affirming strategy' was introduced in the mortuary of a university hospital to enhance respect for the deceased and next-of-kin (NOK). Design: NOK who collected bodies in the mortuary of a university hospital participated in a survey. The satisfaction scores, needs and expectations were compared with a similar survey from 2015. Results: The overall experience for NOK improved significantly compared with 2015. The greatest improvement was achieved in 'mortuary environment', 'attitude of mortuary staff' and 'body viewing arrangement in the mortuary'. The perceived need for additional psychosocial support was significantly reduced. Conclusions: Results demonstrate success of the life-affirming strategy in enhancing end-of-life care for bereaved families. The person-centered approach modernizes and professionalizes mortuary services, with a positive impact on the deceased, NOK, mortuary staff, hospital administration and wider community.

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AIM: Direct kidney involvement in B-cell lymphoproliferative disease is a rare disorder with only a few studies reported in Caucasian patients. The clinicopathological characteristics and outcome of this entity remain poorly described. METHODS: We retrospectively studied all adult Chinese patients who had histology-proven renal parenchymal infiltration by malignant B-cells between 1 January 2000 and 31 December 2018 at two tertiary hospitals in Hong Kong. Clinical, pathological and radiological data were collected from 20 patients. Follow-up data were analysed until 31 December 2019. RESULTS: Median follow-up duration was 22 (1-171) months. Only seven patients (35%) had established diagnosis of haematological cancer before kidney biopsy. Diffuse large B-cell lymphoma (DLBCL) was the most common subtype in our cohort (n = 5, 25%). Others included low-grade B-cell lymphoma (n = 11), intravascular large B-cell lymphoma (n = 1), mantle cell lymphoma (n = 1) and multiple myeloma (n = 2). Fourteen patients (70%) presented with AKI while 12 patients (60%) had proteinuria. Seven patients (35%) had unilateral renal mass, one had bilateral renal masses and one had bilateral diffuse nephromegaly in computed tomography. Lymphomatous tubulointerstitial infiltration was the prevalent histological finding. Nine patients (45%) had coexisting renal lesions other than direct tumour infiltration. All but one patient received chemotherapy. Ten patients died and renal responders had a significantly better survival than non-renal responders (p = .03). CONCLUSION: Direct tumour infiltration can occur in a wide variety of B-cell lymphoproliferative disorders. Coexisting immunoglobulin-related nephropathy is frequently found. Renal biopsy is required for early diagnosis which allows timely and appropriate treatment.

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CASE PRESENTATION: A 47-year-old woman was admitted to the hospital for an episode of hemoptysis. She coughed out small amount of clotted blood the morning of admission. She had no other symptoms on further review. Her medical history was unremarkable with the exception of an upper respiratory tract infection 9 months previously. She did not have any significant medical history or recent sick contacts. She was a lifelong nonsmoker and the mother of three teenaged children. She had irregular menses for the past 2 years, and her last menstrual period was 3 months ago. She reliably reported not engaging in any sexual contact for the past 2 years.

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OBJECTIVE: Renal thrombotic microangiopathy (TMA) is an uncommon pathological finding in lupus nephritis (LN), and its clinical significance remains to be defined. METHODS: Twenty-four patients with lupus nephritis (LN) and renal TMA were selected from a retrospective review of 677 biopsy-proven LN patients, and compared with 48 LN controls without TMA (1:2 ratio) matched according to demographics and treatments. RESULTS: Renal TMA was noted in 3.5% of kidney biopsies of LN. TMA was associated with a higher prevalence of anti-Ro (45.8% vs 18.8%; p = 0.016), higher Systemic Lupus Erythematosus Disease Activity Index scores (21.4 ± 8.5 vs 10.8 ± 2.3; p < 0.001), lower estimated glomerular filtration rate (eGFR; 16.8 ± 11.7 ml/min vs 77.8 ± 28.6 ml/min; p < 0.001), and a higher percentage of patients who required dialysis (37.5% vs 2.1%; p < 0.001) at the time of kidney biopsy. Activity and chronicity indices [median (range)] were higher in the TMA group [11 (2-19) and 3 (1-8), respectively, compared with 7 (0-15) and 1 (0-3) in controls; p = 0.004 and p < 0.001; respectively]. Patients with TMA showed inferior 5-year renal survival and higher incidence of chronic kidney disease at last followup (70% and 66.6%, respectively, compared with 95% and 29.2% in controls; p = 0.023 and 0.002, respectively). The TMA group also showed lower median eGFR compared with controls [50.1 (IQR 7-132) ml/min vs 85.0 (IQR 12-147) ml/min; p = 0.003]. Five-year patient survival rate was similar between the 2 groups (87% and 98% in TMA and control group, respectively; p = 0.127). CONCLUSION: TMA in kidney biopsy was associated with more severe clinical and histological activity, and significantly inferior longterm renal outcome in LN.

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Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant renal disease with incomplete penetrance, associated with specific protein-modifying mutations in the APOE gene. LPG is associated with poor renal prognosis, in which lipoprotein thrombi are seen in the glomerular capillaries. Dyslipidemia in LPG generally resembles type III hyperlipoproteinemia with elevated serum apolipoprotein E level. Fibrate is the most frequently reported lipid-lowering therapy in LPG as hypertriglyceridemia is common in these individuals. There are few existing case reports on effectiveness of statin monotherapy for LPG. We report a 32-year-old Chinese man who presented with nephrotic syndrome, renal impairment, severe hypercholesterolemia without hypertriglyceridemia, and hypertension. Renal biopsy confirmed lipoprotein glomerulopathy. Genetic testing confirmed APOE Kyoto mutation. Anti-hypertensive therapy, including angiotensin receptor blocker, and statin were initiated. Concomitant with normalization of lipid profile, his proteinuria markedly improved, and his renal function has remained stable up to 3 years, demonstrating sustained benefit with statin monotherapy in LPG.

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AIM: Accumulating literature indicates that late acute rejection (LAR) after kidney transplantation portends an unfavourable prognosis. There are no data on the incidence of LAR in Asian subjects, or its risk factors and associated clinical outcomes. METHODS: We conducted a retrospective single-centre case-+control study to investigate the incidence, risk factors and prognosis of LAR in Chinese kidney transplant recipients. Subjects with or without LAR were matched for age, gender, era of transplantation, allograft type, and maintenance immunosuppression regimen. RESULTS: Thirty-two episodes of LAR occurred within an observation period of 12 years giving an incidence rate of 0.46 episodes per 1000 patient-years. Acute rejection within the first year after transplantation was associated with an increased risk of LAR (OR 3.59, P = 0.041). In patients receiving maintenance immunosuppression regimen with steroid, cyclosporin A (CsA) and mycophenolate or an m-TOR inhibitor, patients with LAR showed lower trough CsA levels prior to and at the time of rejection compared to Controls (86.0 ± 26.1 vs. 105.6 ± 13.3 µg/L, P = 0.049; and 75.7 ± 35.7 vs. 106.0 ± 20.5 µg/L, P = 0.032, respectively). Trough CsA level below 80 µg/L was associated with the development of LAR (OR 10.82, P = 0.032). Patients with LAR showed an inferior allograft survival (P < 0.001) while patient survival rates were similar (P = 0.122). CONCLUSIONS: Late acute rejection is uncommon in Chinese kidney transplant recipients but is associated with reduced allograft survival. Risk factors include acute rejection in the first post-transplant year and trough CsA level below 80 µg/L in patients on CsA-based maintenance immunosuppression. Minimization of immunosuppression in apparently stable kidney transplant recipients must be exercised with caution.

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BACKGROUND: Urine from kidney transplant recipient has proven to be a viable source for donor DNA. However, an optimized protocol would be required to determine mis-matched donor HLA specificities in view of the scarcity of DNA obtained in some cases. METHODS: In this study, fresh early morning urine specimens were obtained from 155 kidney transplant recipients with known donor HLA phenotype. DNA was extracted and typing of HLA-A, B and DRB1 loci by polymerase chain reaction-specific sequence primers was performed using tailor-made condition according to the concentration of extracted DNA. RESULTS: HLA typing of DNA extracted from urine revealed both recipient and donor HLA phenotypes, allowing the deduction of the unknown donor HLA and hence the degree of HLA mis-match. By adopting the modified procedures, mis-matched donor HLA phenotypes were successfully deduced in all of 35 tested urine samples at DNA quantities spanning the range of 620-24,000 ng. CONCLUSIONS: This urine-based method offers a promising and reliable non-invasive means for the identification of mis-matched donor HLA antigens in kidney transplant recipients with unknown donor HLA phenotype or otherwise inadequate donor information.

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JC virus (JCV)-associated nephropathy has been increasingly recognized as a cause of allograft dysfunction with graft loss in renal transplant recipients. Like many other opportunistic viral infections in transplant recipients, there are currently limited therapeutic options for this condition. Fusidic acid has previously been reported to exhibit antiviral activity against JCV in in vitro assays. We report the first in vivo study to document the rapid reduction of JC viruria and stabilization of allograft function by oral fusidic acid (fusidate sodium) in a deceased donor renal transplant recipient with JCV-associated nephropathy and acute allograft dysfunction which did not improve initially to surgical relief of hydronephrosis and reduction of immunosuppressants. Rapid reduction of JC viruria detected by quantitative PCR and stabilization of renal function were observed. Fusidic acid has several practical advantages in this clinical setting, including a low EC50 against JCV, high plasma C max, long half-life, availability of both oral and intravenous formulations, excellent oral bioavailability, good patient tolerability, and lack of serious drug interactions with other drugs taken by renal transplant recipients. Further mechanistic and clinical studies are necessary to evaluate this treatment option for JCV-associated nephropathy.

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Structure analysis using X-ray and neutron powder diffraction and elemental mapping has been used to demonstrate that nominal A-site deficient Sr(2-x)FeMoO(6-δ) (0 ≤x≤ 0.5) compositions form as Mo-rich Sr(2)Fe(1-y)Mo(1+y)O(6) (0 ≤y≤ 0.2) perovskites at high temperatures and under reducing atmospheres. These materials show a gradual transition from the Fe and Mo rock salt ordered double perovskite structure to a B-site disordered arrangement. Analysis of the fractions of B-O-B' linkages revealed a gradual increase in the number of Mo-O-Mo linkages at the expense of the ferrimagnetic (FIM) Fe-O-Mo linkages that dominate the y = 0 material. All samples contain about 10-15% antiferromagnetic (AF) Fe-O-Fe linkages, independent of the degree of B-site ordering. The magnetic susceptibility of the y = 0.2 sample is characteristic of a small domain ferrimagnet (T(c)∼ 250 K), while room temperature neutron powder diffraction demonstrated the presence of G-type AF ordering linked to the Fe-O-Fe linkages (m(Fe) = 1.25(7)µ(B)). The high temperature thermoelectric properties are characteristic of a metal with a linear temperature dependence of the Seebeck coefficient, S (for all y) and electrical resistivity ρ (y≥ 0.1). The largest thermoelectric power factor S(2)/ρ = 0.12 mW m(-1) K(-1) is observed for Sr(2)FeMoO(6) at 1000 K.

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INTRODUCTION: Myeloma-associated glomerulopathy could mimic idiopathic minimal change nephropathy, which poses a diagnostic challenge to nephrologists. CASE REPORT: A 60-year-old patient presented with nephrotic range of proteinuria. Serum creatinine level was normal. Immune markers and tumor markers were unrevealing. No monoclonal protein was detected on serum protein electrophoresis. Renal biopsy showed marked effacement of foot processes and no evidence of immunoglobulin or amyloid deposition on electron microscopy/immunofluorescence staining, compatible with idiopathic minimal change nephropathy histologically. However, proteinuria persisted despite steroid treatment. In view of the atypical course of the disease, workup for secondary glomerulopathy was repeated and paraproteinuria was unexpectedly found. Subsequent bone marrow examination confirmed light chain myeloma. CONCLUSION: Urine protein electrophoresis and serum/urine immunofixation are useful tests to detect the monoclonal protein in suspicious cases.

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OBJECTIVE: To perform a clinicopathological study of patients having renal biopsies after liver transplantation. DESIGN: Case series. SETTING; Queen Mary Hospital, Hong Kong. PATIENTS: All post-liver transplantation patients who had a renal biopsy in the period from January 2000 to December 2010. RESULTS: Eleven renal biopsies were retrieved for review from 10 patients with liver transplantation. The male-to-female ratio was 9:1 (age range, 47-63 years). The median liver transplant-to-renal biopsy interval was 1590 (range, 102-3699) days. The predominant histological changes were interstitial fibrosis and tubular atrophy. Diabetic nephropathy (n=6) and immunoglobulin A nephropathy (n=4) were the commonest glomerulopathies. Only one patient had chronic calcineurin inhibitor nephrotoxicity. With a mean follow-up of 53 months, three patients died 2 to 53 months post-renal biopsy. All surviving patients had chronic renal impairment. Five patients developed end-stage renal failure and four had significant persistent proteinuria. CONCLUSION: Renal pathology was variable after liver transplantation; most biopsies showed complex renal lesions, whilst calcineurin inhibitor nephrotoxicity was rare. The recognition of kidney histology attributable to metabolic derangements after liver transplantation is potentially important in the interpretation of renal biopsy specimens and patient management. The renal outlook of this group of patients is guarded.

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