Successful Renal Transplant in Castleman Disease - First Case Report from India.

Castleman disease (CD) comprises a rare group of heterogenous benign lymphoproliferative disorders with pathologic similarities. However, they present with diverse clinical manifestations. Renal involvement is rare in CD and is mainly reported with plasma cell type of multicentric disease. Various glomerular pathologies, interstitial involvement, or thrombotic microangiopathies have all been reported, some of which progress to end-stage renal disease (ESRD). Progression of CD to ESRD is well documented; however, a patient on dialysis developing CD is rare. Moreover, kidney transplantations have seldom been performed on patients with CD. We report a patient with ESRD of unknown etiology who developed multicentric CD while on dialysis. He was treated with four doses of rituximab and later underwent a living kidney transplant with his wife as a donor. He has been clinically well ever since. We believe that this is possibly the first successful case of renal transplantation in CD with ESRD being reported from India.

Exploring urinary extracellular vesicles for organ transplant monitoring: A comprehensive study for detection of allograft dysfunction using immune-specific markers.

BACKGROUND: Allograft dysfunction (AGD) is a common complication following solid organ transplantation (SOT). This study leverages the potential of urinary extracellular vesicles (UEVs) for the non-invasive detection of AGD. AIM: We aimed to assess the diagnostic value of T-cell and B-cell markers characteristic of T-cell-mediated and antibody-mediated rejection in UEV-mRNA using renal transplantation as a model. MATERIALS AND METHODS: UEVs were isolated from 123 participants, spanning healthy controls, functional transplant recipients, and biopsy-proven AGD patients. T-cell and B-cell marker mRNA expressions were evaluated using RT-qPCR. RESULTS: We observed significant differences in marker expression between healthy controls and AGD patients. ROC analysis revealed an AUC of 0.80 for T-cell markers, 0.98 for B-cell markers, and 0.94 for combined markers. T-cell markers achieved 81.3 % sensitivity, 80 % specificity, and 80.4 % efficiency. A triad of T-cell markers (PRF1, OX40, and CD3e) increased sensitivity to 87.5 % and efficiency to 82.1 %. B-cell markers (CD20, CXCL3, CD46, and CF3) delivered 100 % sensitivity and 97.5 % specificity. The combined gene signature of T-cell and B-cell markers offered 93.8 % sensitivity and 95 % specificity. CONCLUSION: Our findings underscore the diagnostic potential of UEV-derived mRNA markers for T-cells and B-cells in AGD, suggesting a promising non-invasive strategy for monitoring graft health.

Cardiorenal disease management in type 2 diabetes: An expert consensus.

BACKGROUND AND AIM: The interplay between cardiovascular disease (CVD), chronic kidney disease (CKD) and type 2 diabetes (T2D) is well established. We aim at providing an evidence-based expert opinion regarding the prevention and treatment of both heart failure (HF) and renal complications in people with T2D. METHOD: ology: The consensus recommendations were developed by subject experts in endocrinology, cardiology, and nephrology. The criteria for consensus were set to statements with ≥80% of agreement among clinicians specialized in endocrinology, cardiology, and nephrology. Key expert opinions were formulated based on scientific evidence and clinical judgment. RESULTS: Assessing the risk factors of CVD or CKD in people with diabetes and taking measures to prevent HF or kidney disease are essential. Known CVD or CKD among people with diabetes confers a very high risk for recurrent CVD. Metformin plus lifestyle modification should be the first-line therapy (unless contraindicated) for the management of T2D. Glucagon-like peptide 1 (GLP-1) agonists can be preferred in people with atherosclerotic cardiovascular disease (ASCVD) or with high-risk indicators, along with sodium-glucose cotransporter-2 inhibitors (SGLT2i), whereas SGLT2i are the first choice in HF and CKD. The GLP-1 agonists can be used in people with CKD if SGLT2i are not tolerated. CONCLUSION: Current evidence suggests SGLT2i as preferred agents among people with T2D and HF, and for those with T2D and ASCVD. SGLT2i and GLP-1RA also lower CV outcomes in those with diabetes and ASCVD, and the treatment choice should depend on the patient profile.

Identifying stable reference genes in polyethene glycol precipitated urinary extracellular vesicles for RT-qPCR-based gene expression studies in renal graft dysfunction patients.

BACKGROUND: Urinary extracellular vesicles (UEVs) hold RNA in their cargo and are potential sources of biomarkers for gene expression studies. The most used technique for gene-expression studies is quantitative polymerase chain reaction (qPCR). It is critical to use stable reference genes (RGs) as internal controls for normalising gene expression data, which aren't currently available for UEVs. METHODS: UEVs were precipitated from urine of graft dysfunction patients and healthy controls by Polyethylene glycol, Mn6000 (PEG6K). Vesicular characterisation confirmed the presence of UEVs. Gene expression levels of five commonly used RGs, i.e., Beta-2-Microglobulin (B2M), ribosomal-protein-L13a (RPL13A), Peptidylprolyl-Isomerase-A (PPIA), hydroxymethylbilane synthase (HMBS), and glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) were quantified, and their stability was established through the RefFinder. The stability of identified RGs was validated by quantification of Perforin and granzyme B, signature molecules of renal graft dysfunction. RESULTS: Urine precipitated with 12% 6 K PEG yielded round and double-membraned UEVs of size ranging from 30 to 100 nm, as confirmed through transmission electron microscopy. Nanoparticle tracking analysis (59 ± 22 nm) and Dynamic-light-scattering (78 ± 56.5 nm) confirmed their size profile. Semi-quantitative Exocheck antibody array demonstrated the presence of EV protein markers in UEV. Using the comparative ΔCт method and RefFinder analysis, B2M (1.6) and RPL13A (1.8) genes emerged as the most stable reference genes. Validation of target gene expression in renal graft dysfunction patients confirmed the efficiency of B2M and RPL13A through significant upregulation compared to other RGs. CONCLUSIONS: Our study identified and validated B2M and RPL13A as optimal RGs for mRNA quantification studies in the UEVs of patients with renal graft dysfunction.

Anti-glomerular Basement Membrane Disease with Atypical Associations.

Anti-glomerular basement membrane (anti-GBM) disease is a systemic autoimmune disorder characterized by circulating immunoglobulin (Ig) G antibodies to carboxy-terminal, noncollagenous 1 domain of type IV collagen of GBM. Patients typically present with rapidly progressive glomerulonephritis and pulmonary hemorrhage. Anti-GBM disease has been reported to coexist with pauci-immune antineutrophil cytoplasmic autoantibody-positive glomerulonephritis and membranous glomerulopathy. The presentation of anti-GBM disease with thrombotic microangiopathy (TMA) and IgA nephropathy has been rarely described. We herein report two cases of anti-GBM antibody disease, both with crescentic glomerulonephritis and peripheral linear deposits of IgG, one case with clinical and histological findings of associated TMA and other with findings of extensive mesangial IgA deposits. Both the patients were treated with corticosteroid, intravenous cyclophosphamide, and plasma exchange but had poor renal recovery. Association of anti-GBM disease with TMA or IgA nephropathy could open up new pathogenetic mechanism and may help us to prognosticate anti-GBM disease.

Sociodemographic profile of breast cancer patients diagnosed by FNAC.

The study included 431 patients who underwent breast FNAC over a period of five years between 2003 and 2008. The required clinical details were obtained from the requisition forms. The Information about the level of education and occupation were collected by interviewing the subjects. The number of cases of breast carcinoma was significant constituting 14.84% (n = 64). The study showed that the peak age for breast carcinoma was between 41 and 50 years. This correlates with the national figure where most of the cases observed belonged to the reproductive age group. Most of the females were married (93.75%) and were multiparous (92.18%). Maximum number of patients had only received primary education. There was not much difference in the number regarding whether they lived in urban or rural areas. Middle and lower socioeconomic class contributed the bulk of the cases and it were the housewives who were in majority (85.93%).

Management of large amoebic liver abscess--a comparative study of needle aspiration and catheter drainage.

Amoebiasis in endemic in the tropical countries with amoebic liver abscesses being a common complication. Different modalities of treatment of amoebic liver abscess are conservative (medical management), percutaneous needle aspiration, percutaneous catheter drainage, surgical drainage and endoscopic drainage. This study was carried out to compare the efficacy, safety and outcome of needle aspiration comparing with percutaneous catheter drainage of large (> or = 5cm diameter) amoebic liver abscesses. This was a prospective study carried over a period of two years (2006-2008) at the general surgery department of Calcutta National Medical College and Hospital, Kolkata. A total of 45 patients were included in this study. All of them had amoebic liver abscess with diameter of abscess cavity > or = 5cm. They were divided into two groups. Group A included 22 patients and they were treated with needle aspiration. Group B included 23 patients and they were treated by catheter drainage. Improvement in clinical features, liver function tests, ultrasonic evidence of decrease in the size of abscess cavity was considered as criteria for successful treatment. The sex ratio and the age incidence in the two groups were similar. In about 80% patients the right lobe was affected, in about 18% the left lobe was affected and in rest the abscess involved both lobes. Needle aspiration was successful in 15 (68.2%) and catheter drainage was successful in 23 patients (100%). The mean hospital stay of patients treated with needle aspiration was more than those treated with catheter drainage. The mean time in days taken for 50% decrease in the size of abscess cavity was significantly greater in group treated with needle aspiration than in those treated with catheter drainage (9 days versus 4 days). It is concluded that percutaneous catheter drainage is more effective in management of large amoebic liver abscess than needle aspiration.

A clinical and pathological study of triple negative breast carcinoma: experience of a tertiary care centre in eastern India.

Breast cancers which do not express oestrogen, progesterone, or HER-2 neu receptors are known as triple negative breast carcinomas. In western literature they have been found to be extremely aggressive with a poor prognosis. However there is scarcity of data regarding this variety of breast cancer in India.To examine the clinical and pathological character of triple negative breast carcinomas and to compare their characteristics with other variants of breast carcinomas which presented to Medical College, Kolkata, a randomised sample of 72 patients were included with breast cancer attending the department of surgery from January 2008 to June 2008.The clinical and histopathological data along with ER/PR status and HER-2 neu expression examined by immunohistochemical methods were recorded.Twenty patients (27.78%) were found to be triple negative.The mean age at presentation was 35.4 +/- 1.95 years with 17 (85%) out of 20 being premenopausal. At presentation, mean tumour size was 4.7 +/- 0.21 cm. Though 15 patients (75%) presented with stage III disease and 16 patients (80%) had grade III histology, 14 (70%) were node negative and 20 (80%) did not have involvement of nipple areola complex and 19(95%) did not have multicentric disease. Triple negative breast cancer is prevalent in eastern India.They are locally aggressive, common in premenopausal women, but strangely do not tend to present with lymph node involvement or involvement of nipple areola complex. Therefore a more conservative approach might have a role in these seemingly aggressive tumours.

Efferent loop gastrojejunal intussusception: a case report.

Gastrojejunal intussusception is a rare complication of gastric surgery. It can occur in cases with gastrojejunostomy done after partial gastric resection or in cases of simple gastrojejunostomy. There are only few cases reported worldwide, Review of literature showed about 200 cases reported till 2006 and a few more cases reported after that. A rare case of retrograde gastrojejunal intussusception is reported. The patient presented in the emergency with severe pain upper abdomen and haematemesis. Contrast enhanced CT scan of abdomen showed hugely distended stomach with retrograde gastrojejunal intussusception on laparotomy, the intussusception was reduced. A jejunojejunostomy was done. The patient is doing well after 1 1/2, months.

Nephrogenic systemic fibrosis following hair-dye ingestion induced acute renal failure.

We report a patient who developed acute renal failure following the ingestion of a hair-dye with a suicidal intent. He was managed by hemodialysis and other symptomatic measures. He developed generalized seizures and underwent MRI scan of the brain using gadolinium containing contrast material followed by development of bilateral and symmetrical thickening and induration of the skin over the extremities and verrucous papules and plaques over the lower back. Skin biopsy and immunohistochemistry showed typical features of nephrogenic fibrosing dermopathy as well as deposits of calcium. Successful management of renal failure resulted in clearing of all skin lesions except a small bony hard plate like area overt the left leg, the biopsy of which showed features of osseous metaplasia.

Anti-GBM antibody disease sans crescents with thrombotic microangiopathy.

We report a case of a 38-year-old male with acute renal failure, elevated anti-glomerular basement membrane (anti-GBM) antibody titres, bilateral nodular lung opacities and hypertension. In the renal biopsy examination, whereas direct immunofluorescence revealed significant peripheral linear deposits of IgG typical of anti-GBM antibody disease (Goodpasture's disease), eosin-haemotoxylin staining showed glomerular and vascular changes typical of thrombotic microangiopathy (TMA) and without crescents. We postulate that the TMA was responsible for the acute renal failure and that antibodies, though demonstrable, were not adequate at the site of the glomerular basement membrane to elicit a crescentic response, because of occlusion of the vascular lumina by the thrombotic process. The patient remained dialysis dependent at a 3-month follow-up.

Causes of death in older peritoneal dialysis patients--can we depend on registry reports?

OBJECTIVES: Despite significant improvements in renal management the mortality associated with dialysis care remains high. Many renal registries report mortality statistics on an annual basis. The objectives of this study were (1) to establish the accuracy of the registered cause of death (CoD) against that determined by a panel of physicians; and (2) to test the feasibility of using the HEMO study CoD classification system in patients on peritoneal dialysis (PD). SETTING: Single centre tertiary-care hospital. PATIENTS AND METHODS: Patients were selected from those aged > or = 65 years who died while receiving PD. The CoD was identified from that registered with the local renal registry, and from clinical records. MAIN OUTCOME MEASURES: (1) Sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV) and kappa score comparing registered and extracted CoD. (2) The proportions of deaths in seven categories using two classification systems. RESULTS: A total of 51 patient charts were reviewed. The agreement between the registered and extracted CoD was poor for all causes of death except malignancy. Kappa scores ranged from 0.55 to 1.0 for different causes. PPV were poor for all except malignancy. Comparison of the CoD was highly dependent on the classification method used (e.g., death secondary to infection was 4% and 25% for CORR and HEMO, respectively). CONCLUSIONS: The registered CoD for patients who die while on PD is often inaccurate. Different policies for classifying deaths can have a significant effect on the final reports, which show the proportion of deaths attributed to different diseases. Standardization across registries is required.