Bladder lesions as incidental findings during transurethral resection of the prostate: prevalence, diagnosis, and pathological findings.

PURPOSE: The purpose of this study was to determine the prevalence of bladder lesions diagnosed during transurethral resection of the prostate (TURP), to identify the associated risk factors, and to correlate the macroscopic descriptions with the pathological findings. METHODS: This was a single-center retrospective case series conducted at a hospital in the city of São Paulo, Brazil. We reviewed the medical and surgical records of patients who underwent TURP between January 2012 and December 2017. RESULTS: The final sample comprised 513 patients, with a mean age of 70.8 years. Bladder lesions were identified during TURP in 109 (21.2%) of the patients, and 90 of those lesions were submitted for pathological examination. The most common macroscopic finding was bullous edema, which was seen in 57 (63.3%) of the 90 lesions examined. The pathological analysis revealed chronic cystitis in 61 lesions (67.8%) and malignant lesions in 16 (17.8%). Of the 57 lesions described as bullous edema, 5 (8.8%) were found to be malignant. CONCLUSIONS: Alterations in the bladder mucosa appear to be more common among elderly patients who use an indwelling urinary catheter for a prolonged period and among patients with recurrent urinary tract infections. In addition, the risk of a bladder lesion being malignant is apparently higher in current and former smokers than in never smokers. Our findings suggest that at-risk patients should undergo biopsy or resection of incidental bladder lesions even if those lesions seem to be benign, due to the low level of agreement between the visual analysis and the pathological examination.

Serum levels of fibroblast growth factor 23 are elevated in patients with active Lupus nephritis.

BACKGROUND: Fibroblast growth factor 23 (FGF23), a phosphate-regulating hormone is an established cardiovascular risk factor. Recently, FGF23 has been related to inflammation. Lupus is an inflammatory disease, and whether FGF23 is associated with Lupus nephritis (LN) activity is unknown. MATERIALS AND METHODS: We studied 15 pre-menopausal patients with recent LN diagnose (⩽2months) and compared them to 1:1 age-matched healthy control group. We measured serum levels of intact FGF23, interleukin-6 (IL-6), tumor necrosis factor α (TNFα), and urinary levels of monocyte chemotactic protein (MCP1). RESULTS: LN patients (29.5±10years) presented proteinuria of 4.7±2.9g/day, and estimated glomerular filtration rate of 37 (31-87)ml/min/1.73m2. They demonstrated higher FGF23 levels when compared to healthy controls [106.7 (80.3-179) vs. 33.6 (25.8-60.9) pg/ml, p<0.001]. FGF23 levels correlated with urinary MCP1 (r=0.62, p<0.001), serum TNFα (r=0.58, p<0.001) and serum IL-6 (r=0.46, p=0.01). Only the correlation between FGF23 and MCP1 remained significant after adjustments for 25(OH) vitamin D and renal function. CONCLUSION: Newly diagnosed LN patients demonstrated elevated FGF23 levels that were positively correlated to urinary MCP1, independently of vitamin D levels and kidney function. If FGF23 may predict clinical outcomes in LN warrants further evaluation.

Schistosoma mansoni infection as a trigger to collapsing glomerulopathy in a patient with high-risk APOL1 genotype.

BACKGROUND: Schistosoma mansoni schistosomiasis (SM) remains a public health problem in Brazil. Renal involvement is classically manifested as a glomerulopathy, most often membranoproliferative glomerulonephritis or focal and segmental glomerulosclerosis. We report a case of collapsing glomerulopathy (CG) associated with SM and high-risk APOL1 genotype (HRG). CASE REPORT: A 35-year-old male was admitted for hypertension and an eight-month history of lower-limb edema, foamy urine, and increased abdominal girth. He had a recent diagnosis of hepatosplenic SM, treated with praziquantel, without clinical improvement. Laboratory tests revealed serum creatinine 1.89mg/dL, blood urea nitrogen (BUN) 24mg/dL, albumin 1.9g/dL, cholesterol 531mg/dL, low-density lipoprotein 426mg/dL, platelets 115000/mm3, normal C3/C4, antinuclear antibody (ANA), rheumatoid factor (RF), and antineutrophil cytoplasmic antibodies (ANCA), negative serologies for hepatitis C virus (HCV) and human immunodeficiency virus (HIV), HBsAg negative and AntiHBc IgG positive, no hematuria or leukocyturia, 24 hour proteinuria 6.56g and negative serum and urinary immunofixation. Kidney biopsy established the diagnosis of CG. A treatment with prednisone was started without therapeutic response, progressing to end-stage kidney disease 19 months later. Molecular genetics investigation revealed an HRG. CONCLUSIONS: This is the first report of CG associated with SM in the setting of an HRG. This case highlights the two-hit model as a mechanism for CG pathogenesis, where the high-risk APOL1 genotype exerts a susceptibility role and SM infection serves as a trigger to CG.

Evidences of histologic thrombotic microangiopathy and the impact in renal outcomes of patients with IgA nephropathy.

INTRODUCTION: IgA nephropathy (IgAN) is the most common primary glomerulopathy worldwide. According to the Oxford Classification, changes in the kidney vascular compartment are not related with worse outcomes. This paper aims to assess the impact of thrombotic microangiopathy (TMA) in the outcomes of Brazilian patients with IgAN. MATERIALS AND METHODS: Analysis of clinical data and kidney biopsy findings from patients with IgAN to assess the impact of TMA on renal outcomes. RESULTS: The majority of the 118 patients included were females (54.3%); mean age of 33 years (25;43); hypertension and hematuria were observed in 67.8% and 89.8%, respectively. Median creatinine: 1.45mg/dL; eGFR: 48.8ml/min/1.73m2; 24-hour proteinuria: 2.01g; low serum C3: 12.5%. Regarding to Oxford Classification: M1: 76.3%; E1: 35.6%; S1: 70.3%; T1/T2: 38.3%; C1/C2: 28.8%. Average follow-up: 65 months. Histologic evidence of TMA were detected in 21 (17.8%) patients and those ones presented more frequently hypertension (100% vs. 61%, p <0.0001), hematuria (100% vs 87.6%, p = 0.0001), worse creatinine levels (3.8 vs. 1.38 mg/dL, p = 0.0001), eGFR (18 vs. 60 ml/min/1.73m2), p = 0.0001), low serum C3 (28.5% vs. 10.4%, p = 0.003), lower hemoglobin levels (10.6 vs. 12.7g/dL, p<0.001) and platelet counts (207,000 vs. 267,000, p = 0.001). Biopsy findings of individuals with TMA revealed only greater proportions of E1 (68% vs. 32%, p = 0.002). Individuals with TMA were followed for less time (7 vs. 65 months, p<0.0001) since they progressed more frequently to chronic kidney disease (CKD) requiring kidney replacement therapy (KRT) (71.4% vs. 21,6%, p<0.0001). Male sex, T1/T2, and TMA were independently associated with progression to CKD-KRT. CONCLUSIONS: In this study patients with TMA had worse clinical manifestations and outcomes. In terms of histologic evidence, E1 distinguished patients with TMA from other patients. Further studies are necessary to analyze the impact of vascular lesions on IgAN prognosis.

Role of renal expression of CD68 in the long-term prognosis of proliferative lupus nephritis.

INTRODUCTION: Renal histology of proliferative lupus nephritis (LN) shows increased macrophage infiltration, but its association with renal outcome is a matter of debate. Here, we investigate the potential relationship that macrophage expression has with renal prognosis in patients with proliferative LN. METHODS: Fifty patients newly diagnosed with proliferative LN were followed for a median of 8 years. Laboratory testing was conducted at diagnosis, after induction therapy and at the final follow-up evaluation. Renal biopsies were obtained at diagnosis and underwent immunohistochemical analysis with anti-CD68 and monocyte chemoattractant protein 1 monoclonal antibodies. Patients were stratified at final follow-up evaluation into glomerular filtration rate (GFR) >60 ml/min/1.73 m2 (non-progressor group; n = 24) and GFR ≤60 ml/min/1.73 m2 (progressor group; n = 26). All patients were treated with prednisone and six pulses of cyclophosphamide on induction therapy. Conventional maintenance therapy was administered in both groups. RESULTS: Compared to progressors, the non-progressor group showed a lower chronicity index (p = 0.01) and fewer CD68-positive cells in the renal tubules (p = 0.01) and particularly in the renal interstitium (p = 0.0003). Baseline and final serum creatinine correlated positively with the chronicity index (r = 0.3, p = 0.01 and r = 0.3, p = 0.04, respectively), and final serum creatinine correlated positively with interstitial expression of CD68 (r = 0.4, p = 0.0006). CONCLUSION: Renal expression of CD68 and the chronicity index are associated with progression to chronic kidney disease in patients with proliferative LN.

Female Patient with Alport Syndrome and Concomitant Membranous Nephropathy: Susceptibility or Association of Two Diseases?

Alport syndrome (AS) is a disorder of collagen IV, a component of glomerular basement membrane (GBM). The association of AS and immunocomplex nephropathies is uncommon. This is a case of a 37-year-old woman with family history of X-linked AS, including 4 affected sons. This patient developed full-blown nephrotic syndrome along a 3-month period, a presentation not consistent with AS progression. This scenario suggested an alternative diagnosis. A kidney biopsy was therefore performed, showing membranous nephropathy (MN) in addition to GBM structural alterations compatible with AS. Whole exome sequencing also confirmed the diagnosis of X-linked AS, revealing a heterozygous pathogenic mutation in COL4A5. While a negative serum anti-phospholipase A2 receptor did not rule out a primary form of MN, it was also uncertain whether positive serologic tests for syphilis could represent a secondary factor. It is currently unknown whether this unusual association represents AS susceptibility to immunocomplex-mediated diseases or simply an association of 2 disorders.

Serum ferritin level remains a reliable marker of bone marrow iron stores evaluated by histomorphometry in hemodialysis patients.

BACKGROUND AND OBJECTIVES: As well as being a marker of body iron stores, serum ferritin (sFerritin) has also been shown to be a marker of inflammation in hemodialysis (HD) patients. The aim of this study was to analyze whether sFerritin is a reliable marker of the iron stores present in bone marrow of HD patients. DESIGN: Histomorphometric analysis of stored transiliac bone biopsies was used to assess iron stores by determining the number of iron-stained cells per square millimeter of bone marrow. RESULTS: In 96 patients, the laboratory parameters were hemoglobin = 11.3 +/- 1.6 g/dl, hematocrit = 34.3 +/- 5%, sFerritin = 609 +/- 305 ng/ml, transferrin saturation = 32.7 +/- 22.5%, and C-reactive protein (CRP) = 0.9 +/- 1.4 mg/dl. sFerritin correlated significantly with CRP, bone marrow iron, and time on HD treatment (P = 0.006, 0.001, and 0.048, respectively). The independent determinants of sFerritin were CRP (beta-coef = 0.26; 95% CI = 24.6 to 132.3) and bone marrow iron (beta-coef = 0.32; 95% CI = 0.54 to 2.09). Bone marrow iron was higher in patients with sFerritin >500 ng/ml than in those with sFerritin < or =500 ng/ml. In the group of patients with sFerritin < or =500 ng/ml, the independent determinant of sFerritin was bone marrow iron (beta-coef = 0.48, 95% CI = 0.48 to 1.78), but in the group of patients with sFerritin >500 ng/ml, no independent determinant of sFerritin was found. CONCLUSIONS: sFerritin adequately reflects iron stores in bone marrow of HD patients.