The exacerbated hypokalemia in membranous glomerulonephritis due to proximal tubular injury: a neglect issue from a case report and literature review.

BACKGROUND: Membranous glomerulonephritis is the most common primary etiology for the nephrotic syndrome in adults. Beyond the clinical hallmark of nephrotic syndrome such as fluid overloading, dyslipidemia and hypoalbuminemia, the dysregulated homeostasis of potassium and its possible mechanism is seldomly discussed, and its association with the clinical course of membranous GN is lacking. CASE PRESENTATION: A 65 year-old female attended to our emergent department for progressive lower leg edema after taking 15-h of flight. Hypoalbuminemia and hyperlipidemia were both noted, and 24-h urinary total protein was up to 17,950 mg/day. Elevated creatin-phospho-kinase developed at the initial presentation with hypokalemia due to excressive renal excretion. Glycosuria without elevated glycated Hemoglobin occurred. The pathology of kidney biopsy revealed subepithelial immunocomplex deposits with spike formation in the electron microscopy and the positive anti-Phosphlipase A2 receptor antibodies(PLA-2R) with hallmark of membranous glomerulonephritis. In the light microscopy, the vacuolization of proximal tubules was noted, which contributed to the potassium wasting. After 1 year following up duration, the patient's proteinuria persisted after maintenance treatment with calcineurin inhibitor. CONCLUSION: Hypokalemia is a neglected issue in the membranous glomerulonephritis. Unlike the previous literature, our patient had the vacuolization of proximal tubule at the initial presentation with hypokalemia, which might contribute the potassium wasting. The proximal tubular damage with hypokalemia might be a predictive factor for membranous glomerulonephritis.

Prognostic significance of heat shock proteins in urothelial carcinoma of the urinary bladder.

AIMS: Heat shock proteins (HSPs) are a group of molecules induced by a variety of environmental and pathophysiological stresses, including cancer. The expression of HSPs has been implicated in the regulation of apoptosis and immunity in neoplasia. The purpose of this study was to evaluate the expression and clinicopathological relevance of several HSPs in urothelial carcinomas of the urinary bladder. METHODS AND RESULTS: Immunohistochemical staining for HSP27, HSP60, HSP70 and HSP90 was performed on samples collected from 744 clinical cases. The results were correlated with clinicopathological characteristics using univariate and multivariate analyses. High expression of HSP70 predicted recurrence of non-muscle-invasive urothelial carcinoma treated by transurethral resection, and low expression of HSP27 correlated with progression and cancer-specific mortality for non-muscle-invasive cancers treated by transurethral resection. Low expression of HSP27 also predicted cancer-specific mortality for patients who underwent cystectomy. CONCLUSIONS: Both HSP27 and HSP70 impact on the biological behaviour of urothelial carcinomas of the urinary bladder. Immunohistochemical assessment of HSPs can provide useful prognostic information that could ultimately help to develop individualized surveillance programmes.

Her2 amplification distinguishes a subset of non-muscle-invasive bladder cancers with a high risk of progression.

BACKGROUND: Several studies have employed immunohistochemistry to detect Her2/neu overexpression in urothelial carcinomas, yielding a tremendous range of positive expression rates. Few studies have examined Her2 status in non-muscle invasive bladder cancer (NMIBC) using fluorescence in situ hybridisation (FISH). AIM: To evaluate Her2 amplification in NMIBC (Ta/T1), to correlate the findings with recurrence and progression, and compare the Her2 status between primary and progressive tumours. METHODS: FISH and immunohistochemistry for Her2/neu were performed on tissue arrays consisting of 36 papillary urothelial neoplasms of low malignant potential (PUNLMPs), 190 low grade urothelial carcinomas (LG-UCs) and 178 high grade urothelial carcinomas (HG-UCs). 32 cases with specimens of both primary and progressive tumours (from Ta/T1 to T2-4) were included for comparative analyses. RESULTS: 16 HG-UCs (9.0%) showed Her2 gene amplification while none of the PUNLMPs and LG-UCs showed this aberration. There was 100% concordance in the status of Her2 amplification between primary and progressive lesions. Immunohistochemistry and FISH results were in closest agreement when overexpression was defined as 50% of tumour cells showing immunoreactivity. The cumulative incidences of recurrence and progression in Her2-amplified HG-UC were significantly higher than in those without amplification. CONCLUSIONS: A subset of high-grade NMIBCs contain Her2 amplification and are associated with markedly aggressive behaviour. Her2 diagnostics are valuable for distinguishing patients who require diligent surveillance and would potentially benefit from anti-Her2 therapies.

Constructing prognostic model incorporating the 2004 WHO/ISUP classification for patients with non-muscle-invasive urothelial tumours of the urinary bladder.

AIM: To construct a prognostic model for recurrence-free survival (RFS), progression-free survival (PFS) and cancer-specific survival (CSS) for patients who have undergone transurethral resection of non-muscle-invasive (pTa/pT1) urinary bladder urothelial tumours. METHODS: 1366 patients who had undergone transurethral resection of primary non-muscle-invasive urothelial tumours (pTa, 891 patients; pT1, 475 patients) confined to the bladder were retrospectively studied. Tumours were classified according to the 2004 WHO/International Society of Urologic Pathology grading system. Kaplan-Meier and stepwise Cox regression models were applied, and 200 bootstrap resamples were used to generate survival estimates and 95% CIs. A nomogram was developed that incorporated significant variables predicting survival. RESULTS: RFS, PFS and CSS probabilities for non-muscle-invasive bladder urothelial tumours were calculated. Incorporating salient prognostic factors (tumour grade, pT stage, patient age, status of intravesical instillation), the model satisfactorily predicted PFS (concordance index=0.79) and CSS (concordance index=0.87). CONCLUSIONS: Robust nomograms were created to predict PFS and CSS. These data provide an overall perspective of disease outcomes which may aid in developing individualised follow-up programmes.

Prognostic significance of the 2004 WHO/ISUP classification for prediction of recurrence, progression, and cancer-specific mortality of non-muscle-invasive urothelial tumors of the urinary bladder: a clinicopathologic study of 1,515 cases.

To verify prognostic significance of the 2004 World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading systems, we retrospectively studied the tumors of 1,515 patients who underwent transurethral resection of primary non-muscle-invasive urothelial tumors (pTa, 1,006 patients; pT1, 509 patients) confined to the bladder. Cases were classified according to the 2004 WHO/ISUP systems as 212 cases of papillary urothelial neoplasm of low malignant potential (PUNLMP), 706 low-grade papillary urothelial carcinomas (LPUCs), and 597 high-grade papillary urothelial carcinomas (HPUCs). PUNLMP showed the statistically significantly lowest recurrence cumulative incidence compared with the other tumor types. There were significant differences and trends for higher progression and cancer-specific mortality cumulative incidence in the following order: PUNLMP, LPUC, pTa HPUC, and pT1 HPUC. No differences of progression and cancer-specific mortality cumulative incidence were found between pTa and pT1 LPUC. Our study validates the usefulness of the 2004 WHO/ISUP system to classify urothelial tumors into prognostically distinct categories that would contribute to the design of therapeutic and monitoring strategies for patients with non-muscle-invasive bladder urothelial tumors.