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Background Mitochondrial dysfunction plays an important role in the pathogenesis and progression of chronic kidney disease (CKD). We study the relation between urinary mitochondrial DNA (mtDNA) levels and renal dysfunction in non-diabetic CKD. Methods We recruited 32 CKD patients (20 had hypertensive nephrosclerosis, 12 had IgA nephropathy). Urinary supernatant mtDNA level was measured and compared to baseline clinical and pathological parameters. The patients were followed 57.8 ± 30.5 months for renal function decline. Results The average urinary supernatant mtDNA level was 222.0 ± 210.3 copy/μL. There was a modest but significant correlation between urinary mtDNA level and proteinuria (Spearman's r = 0.387, p = 0.035), but not any other baseline clinical or pathological parameter. Urinary mtDNA level had a significant inverse correlation with the slope of GFR decline (r = −0.402, p = 0.023). Urinary mtDNA level is a predictor of renal survival even after adjusting for baseline proteinuria with multivariate Cox analysis. In this model, every increase in urinary mtDNA by 100 copy/μL confers a 25.0% increase in risk of doubling of serum creatinine or need of dialysis (95%CI, 0.7% to 55.1%). Conclusion Mitochondrial DNA is readily detectable in the urinary supernatant of non-diabetic CKD, and its level correlates with the rate of renal function decline and predicts the risk of doubling of serum creatinine or need of dialysis. Further studies are needed to determine the value of urinary supernatant mtDNA level as a prognostic indicator of non-diabetic CKD [ABSTRACT FROM AUTHOR]

Background Glomerular and tubulointerstitial fibrosis play important roles in the progression of chronic kidney disease. We determine whether urinary mRNA levels of extracellular matrix proteins reflect the degree of kidney fibrosis and predict renal function decline in adult nephrotic patients. Methods We studied 56 adult nephrotic patients and 20 controls. Urinary mRNA levels of collagen I A1 chain (COL1A1), collagen IV A3 chain (COL4A3), and fibronectin were measured. Results Urinary sediment mRNA levels of COL1A1 and fibronectin were significantly higher in nephrotic patients as compared to the control, irrespective to the pathological diagnosis. Urinary COL1A1 mRNA level correlates with proteinuria, glomerular and interstitial fibrosis, and inversely with estimated glomerular filtration rate (GFR); urinary fibronectin mRNA level significantly correlates with glomerular and interstitial fibrosis, and inversely with estimated GFR. After 42.4 ± 12.6 months follow-up, the rate of GFR decline inversely correlates with urinary mRNA level of COL1A1 (r = − 0.273, p = 0.044). Multivariate analysis confirmed that urinary COL1A1 mRNA level is an independent predictor of serum creatinine doubling or progressing to end stage renal disease; for each 10-fold increase in urinary COL1A1 mRNA level, there is 15.1% excess in risk (95% confidence interval, 1.9% to 30.4%, p = 0.022). Conclusions Urinary COL1A1 mRNA level is elevated in nephrotic patients irrespective to the pathological diagnosis, and it correlates with proteinuria, histological scarring, and inversely with renal function. Furthermore, urinary COL1A1 mRNA level predicts renal function loss during follow-up. Our results suggest that urinary COL1A1 mRNA level may be used for risk stratification of adult nephrotic syndrome. [ABSTRACT FROM AUTHOR]

Abstract: Background: MicroRNAs are a group of non-coding RNA molecules that play important roles in the pathogenesis of various kidney diseases. We investigate the urinary sediment miRNA levels of adult patients with nephrotic syndrome. Methods: We study 20 patients with diabetic glomerulosclerosis (DGS), 21 with minimal change nephropathy (MCN) or focal glomerulosclerosis (FGS), 23 with membranous nephropathy (MGN), and 10 healthy controls. Urinary sediment miRNA levels are quantified. Results: Urinary sediment miR-29a, miR-192, and miR-200c levels were significantly different between diagnosis groups. Post hoc analysis showed that urinary miR-638 level was significantly lower in all causes of nephrotic syndrome than healthy controls, while the DGS group had lower urinary miR-192 level than other diagnosis groups. In contrast, the MCN/FGS group had higher urinary miR-200c level than other diagnosis groups. For each specific pathology group, urinary level of several miRNA targets significantly correlated with kidney function and histological scarring. Conclusions: Urinary miR-29a, miR-192 and miR-200c levels have characteristic alterations among patients with different causes of nephrotic syndrome. Our results suggest that urinary miRNA levels have the potential of being developed as the diagnosis tool and marker of disease severity in adult nephrotic syndrome. [Copyright &y& Elsevier]

Prevalence of silent kidney disease in Hong Kong: The Screening for Hong Kong Asymptomatic Renal Population and Evaluation (SHARE) program. End-stage renal disease (ESRD) is epidemic worldwide. In Hong Kong, the annual incidence of ESRD has risen from 100 pmp (per million population) in 1996 to 140 pmp in 2003. SHARE (Screening for Hong Kong Asymptomatic Renal Population and Evaluation program) is a population-based screening program aimed at identifying the prevalence of unrecognized renal disease in asymptomatic individuals, allowing further evaluation and disease-modifying interventions. From November to December 2003, SHARE was conducted in several large residential communities in Hong Kong. The screening tool included a questionnaire documenting demographics and history or family history of diabetes mellitus (DM), hypertension (HT), and chronic kidney disease (CKD), together with on-site measurements of blood pressure (BP) and urine dipstick for protein, blood, and glucose. There were a total of 1811 participants. One thousand two hundred and one subjects were entered into the final analysis. Among the 1201 who were apparently "healthy" (asymptomatic and without history of DM, HT, or CKD), the prevalence of positive (≥1+) urine dipstick for protein, glucose, blood, protein or blood, any urine abnormality, and HT (BP≥140/90) was 3.2%, 1.7%, 13.8%, 16%, 17.4%, and 8.7%, respectively. Thirty three percent of the age over 60 years old group had either hypertension or urine abnormalities, compared with 24.0% in the 41- to 60-year-old group and 9.7% in the 20- to 40-year-old group. Having a family history of diabetes or hypertension increases the risk of having urine abnormalities, while a family history of hypertension also increases the risk of high blood pressure. It is concluded that subclinical abnormalities in urinalysis or BP readings are prevalent across all age groups in the adult population. An effective screening program at the primary care level that identifies these subjects for further evaluation is warranted, and the public in Hong Kong should be educated toward the significance of such findings in order to have regular health check for asymptomatic renal diseases. [ABSTRACT FROM AUTHOR]

Background The role of microRNA (miRNA) in peritoneal fibrosis and longitudinal change in transport is uncertain. Methods We studied 80 new peritoneal dialysis (PD) patients. Peritoneal transport was determined by standard peritoneal equilibration test (PET) of creatinine at baseline. Based on published literature, PD effluent levels of 10 miRNA targets were quantified. PET and miRNA quantification were repeated one year later in 46 patients. Results Baseline PD effluent levels of all targets tested had modest but significant correlation with peritoneal transport parameters. PD effluent miR-21 and miR-589 levels correlated with dialysate-to-plasma creatinine concentration at 4 h (D/P4) at baseline (r = 0.377, p = 0.001 and r = 0.237, p = 0.037, respectively) and after one year of PD (r = 0.362, p = 0.014 and r = 0.402, p = 0.007). The change in PD effluent − 21 and miR-589 levels over one year correlated with the corresponding change in D/P4 (r = 0.470, p = 0.001 and r = 0.479, p = 0.002). The number of peritonitis episodes during follow up significantly correlated with the change in PD effluent miR-21 (r = 0.387, p = 0.009) and miR-589 (r = 0.336, p = 0.027) levels. There was no significant correlation between PD effluent miRNA level and ultrafiltration volume. Conclusion Amongst the 10 miRNA targets tested, miR-21 and miR-589 showed consistently significant relation with peritoneal transport. Further studies are needed to delineate their mechanisms of regulating peritoneal transport. [ABSTRACT FROM AUTHOR]