Predominant global glomerulosclerosis in patients of upper urinary tract urothelial carcinoma with pre-existing renal function impairment is a predictor of poor renal outcomes.

BACKGROUND: Incidence of renal dysfunction and risks of progression to end-stage renal disease (ESRD) were reported higher in upper urinary tract urothelial carcinoma (UTUC) than in renal cell carcinoma (RCC) patients after unilateral nephrectomy. METHODS: Totally 193 renal cancer patients, including 132 UTUC and 61 RCC, were studied to clarify whether the pathological changes of the kidney remnant removed from nephrectomy and the clinical factors might predict the risk of ESRD. Renal tubulointerstitial (TI) score and global glomerulosclerosis (GGS) rate were examined by one pathologist and two nephrologists independently under same histopathological criteria. RESULTS: The glomerular filtration rates at the time of surgery were lower in UTUC than RCC groups (p < 0.001). Average GGS score and average TI rate were higher in UTUC than in RCC groups (p < 0.001; p < 0.001). Competitive risk factor analysis revealed that abnormal GGS rate not related to age, predominant in UTUC with pre-existing renal function impairment, was a histopathological predictor of poor renal outcomes (creatinine doubling or ESRD) within 5 years in UTUC patients. CONCLUSION: Pre-existing renal function and pathological change of kidney remnant in both UTUC and RCC have the value for prediction of renal outcomes.

High hepatitis B virus surface antigen levels and favorable interleukin 28B genotype predict spontaneous hepatitis C virus clearance in uremic patients.

BACKGROUND & AIMS: Host and viral factors interplay in the spontaneous clearance of hepatitis C virus (HCV) infection. We aimed to explore the roles of IL28B genotypes and hepatitis B virus (HBV) infections in spontaneous HCV seroclearance. METHODS: IL28B rs8099917 genotypes, HCV and HBV markers were determined in 290 patients who were seropositive for HCV antibodies from 1681 total uremic patients on maintenance hemodialysis. RESULTS: Persistent HCV viremia was observed in 74.6% (214/287) of patients. Logistic regression revealed that the strongest factors associated with spontaneous HCV seroclearance were carriage of rs8099917 TT-type (odds ratio/95% confidence intervals [OR/CI]: 6.22/1.41-27.35, p=0.016), followed by concurrent hepatitis B surface antigen (HBsAg) seropositivity (OR/CI: 2.37/1.06-5.26, p=0.035). The clearance rate was highest among patients with both positive HBsAg/rs8099917 TT-type (44.8%, OR/CI: 20.88/3.5-402.5), followed by positive HBsAg/rs8099917 non-TT-type (28.6%, OR/CI: 8.86/1.8-160.8), and negative HBsAg/rs8099917 TT-type (26.7%, OR/CI: 12.75/1.0-319.4), compared to 4% of negative HBsAg/rs8099917 non-TT-type (trend p=0.0002). HBsAg levels, but not HBV DNA levels, were significantly associated with spontaneous HCV seroclearance. Spontaneous HCV seroclearance rate was 58.3% in patients with HBsAg>200IU/ml/rs8099917 TT-type (OR/CI: 42.54/5.7-908.4), 28.0% in patients with HBsAg<200IU/ml/rs8099917 TT-type or HBsAg>200IU/ml/rs8099917 non-TT-type (OR/CI: 11.12/2.3-201.0), compared to only 3.3% in those with HBsAg<200IU/ml/rs8099917 non-TT-type (trend p=0.0004). Five of 214 (2.3%) HCV viremic patients at enrollment had spontaneous HCV seroclearance during one-year follow-up, which was associated with baseline HCV RNA and HBsAg levels. CONCLUSIONS: High HBsAg levels and favorable IL28B genotype were additively associated with spontaneous HCV seroclearance in uremic patients.

The study of interferences for diagnosing albuminuria by matrix-assisted laser desorption ionization/time-of-flight mass spectrometry.

BACKGROUND: Matrix-assisted laser desorption ionization/time-of-flight (MALDI-TOF) mass spectrometric analysis of albumin (ALB) biomarkers is an alternative approach toward the rapid diagnosis of proteinuria for screening a large number of samples. The aim of this study is to reveal if interfering factors in urinary dipstick approach would affect the results of diagnosing albuminuria by MALDI-TOF MS. METHODS: The effects of various interfering chemicals on the diagnosis of albumin in urine were examined using both MALDI-TOF mass spectrometric and dipstick approaches. Semi-quantification of albumin was performed by using MALDI-TOF MS. RESULTS: Interferences from various drugs, detergents, vitamins and their metabolites, alkaline, and blood, which often cause false-positive and false-negative results in conventional urinary dipstick analysis, are avoided when using this MALDI-TOF MS approach. It was found that the intensity of +1 and +2 albumin ions varies with the albumin concentration. A log/log plot of the intensity ratio vs. albumin concentration is then used as a calibration curve for semi-quantifying the albumin in urines. CONCLUSIONS: MALDI-TOF MS is an effective approach toward avoiding interferences caused by various chemical compounds during the rapid diagnosis of albumin in urine. Semi-quantification of albuminuria is also achieved by this MALDI-TOF MS approach.

Association of hyperuricemia with renal outcomes, cardiovascular disease, and mortality.

BACKGROUND AND OBJECTIVES: Hyperuricemia is an independent risk factor for mortality, cardiovascular disease, and renal disease in general population. However, the relationship between hyperuricemia with clinical outcomes in CKD remains controversial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The study investigated the association between uric acid with all-cause mortality, cardiovascular events, renal replacement therapy, and rapid renal progression (the slope of estimated GFR was less than -6 ml/min per 1.73 m(2)/y) in 3303 stages 3-5 CKD patients that were in the integrated CKD care system in one medical center and one regional hospital in southern Taiwan. RESULTS: In all subjects, the mean uric acid level was 7.9 ± 2.0 mg/dl. During a median 2.8-year follow-up, there were 471 (14.3%) deaths, 545 (16.5%) cardiovascular events, 1080 (32.3%) participants commencing renal replacement therapy, and 841 (25.5%) participants with rapid renal progression. Hyperuricemia increased risks for all-cause mortality and cardiovascular events (the adjusted hazard ratios for quartile four versus quartile one of uric acid [95% confidence interval] were 1.85 [1.40-2.44] and 1.42 [1.08-1.86], respectively) but not risks for renal replacement therapy (0.96 [0.79-1.16]) and rapid renal progression (1.30 [0.98-1.73]). CONCLUSIONS: In stages 3-5 CKD, hyperuricemia is a risk factor for all-cause mortality and cardiovascular events but not renal replacement therapy and rapid renal progression.

Association of hsCRP, white blood cell count and ferritin with renal outcome in chronic kidney disease patients.

Inflammation is a pathogenic factor in renal injury, but whether inflammation is related to renal outcome in chronic kidney disease (CKD) patients is little known. We thus assess the association of inflammation and renal outcome in an advanced CKD cohort. This study analyzed the association between inflammatory markers, such as C-reactive protein (hsCRP), white blood cell (WBC) count and ferritin, renal replacement therapy (RRT) and rapid renal progression (estimated GFR slope<-6 ml/min/1.73 m²/y) in 3303 patients with stage 3-5 CKD. In all subjects, the mean hsCRP, WBC count, and ferritin levels were 1.2 (0.4, 5.4) mg/L, 7.2±2.3×10³ cells/µL, and 200 (107,349) ng/mL, respectively. During a mean 3.2-year follow-up, there were 1080 (32.7%) subjects commencing RRT, and 841(25.5%) subjects presenting rapid renal progression. Both hsCRP and ferritin were associated with increased risk for RRT with the adjusted HR (tertile 3 versus tertile 1∶1.17 〔1.01-1.36〕 and 1.20 〔1.03-1.40〕, respectively). Both hsCRP and ferritin were associated with increased odds for rapid renal progression with the adjusted OR (tertile 3 versus tertile 1∶1.40 〔1.13-1.77〕 and 1.32 〔1.06-1.67〕, respectively). hsCRP and ferritin stratified by albumin were also associated with RRT and rapid renal progression. Instead, WBC count was not associated with renal outcome. In conclusion, elevated levels of hsCRP and ferritin are risk factors associated with RRT and rapid renal progression in advanced CKD patients.

Acute cerebral infarction in a patient with nodular glomerulopathy--atypical features and differential diagnosis.

Nodular glomerulopathy is a pattern of glomerular injury observed under light microscopy that could result from several diseases presented as nephrotic syndrome clinically. Compared with venous thrombosis, cerebral infarction resulting from arterial thrombosis is relatively rare in these patients. We report an interesting case of severe nephrotic syndrome complicated with acute cerebral infarction, and renal biopsy revealed nodular glomerulopathy under light microscopy. Immunofluorescent staining was positive for λ light chain (predominant) and κ light chain, mainly in mesangial areas, and electron microscopic study showed massive amorphous acellular deposits also in mesangial areas with some local extension to subendothelial space. Congo red stain gave negative results under polarized light. The case was concluded as an atypical presentation of light chain deposition disease both pathologically and clinically.