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Background: Although urinary angiotensinogen (AGT) and renin reflect intrarenal renin-angiotensin system activity and are enhanced in proteinuric chronic kidney disease, the clinical value of urinary AGT and renin levels during antiproteinuric treatment has yet to be determined. We investigated the clinical usefulness of initial urinary AGT or renin to determine the antiproteinuric effects of angiotensin receptor blockers (ARBs)., Methods: This multicenter, prospective, single-arm study included 205 patients with overt proteinuria (urinary protein/creatinine ratio [uPCR] ≥ 1 mg/mg) enrolled between April 2009 and December 2011. All patients were treated with valsartan. The urinary AGT/creatinine ratio (uAGT/Cr) was measured at the baseline and 24 weeks, and the renin/creatinine ratio (uR/Cr) was measured at the baseline. Fifty-six patients were followed-up for 5 years., Results: The mean age was 47.6 years and 51.2% were male. The mean uPCR was 2.32 mg/mg and the mean eGFR was 63.2 mL/min/1.73m 2 . Natural logarithms (ln) (uAGT/Cr), ln(uR/Cr), and diabetes mellitus were associated with proteinuria decrement (decrease in uPCR ≥1 mg/mg). Ln(uAGT/Cr) was an independent predictor for proteinuria decrement (OR 1.372, 95% CI, 1.068-1.762, P = 0.013). Among the 56 patients followed-up for 5 years, Δln(uAGT/Cr) at 24 weeks was an independent predictor for uPCR < 1 mg/mg at 5 years (OR 0.379, 95% CI, 0.20-0.715, P = 0.003)., Conclusions: Our study demonstrates the potential role of both baseline urinary AGT and changes in urinary AGT during the initial 24 weeks as surrogate markers predicting the antiproteinuric effects of ARBs in patients with overt proteinuria.

This study aimed to investigate the association of nonalcoholic fatty liver disease (NAFLD) and its severity with the decline in kidney function in patients with chronic kidney disease (CKD). We conducted a cohort study of 1,525 CKD patients who underwent repeated health check-up examinations from January 2003 through December 2013. NAFLD was diagnosed by ultrasonography and its severity was assessed by the NAFLD fibrosis score. At baseline, the prevalence of NAFLD was 40.9%, and the mean estimated glomerular filtration rate (eGFR) was 59.1 ml/min/1.73 m 2 . The average follow-up was 6.5 years. The age- and sex-adjusted decline in eGFR was greater in patients with NAFLD (-0.79% per year, 95% CI -1.31%, -0.27%) compared to those without it (0.30%, 95% CI -0.14%, 0.76%; p = 0.002). In multivariable adjusted models, the average difference in annual percent change in decline in eGFR comparing patients with NAFLD to those without NAFLD was -1.06% (-1.73%, -0.38%; p = 0.002). The decline in eGFR associated with NAFLD was greater in patients with higher NAFLD fibrosis score, in those with proteinuria or with low eGFR at baseline ( <45 ml/min/1.73 m 2 ), and in those who were smokers and hypertensive. Therefore, NAFLD is independently associated with CKD progression.

Aim: The intrarenal renin-angiotensin system (RAS) has been reported to be activated in chronic proteinuria patients. This study aimed to compare intrarenal RAS activity between diabetic nephropathy (DN) and non-diabetic nephropathy (NDN) patients with overt proteinuria., Methods: A multicenter, cross-sectional study was conducted in 116 patients with overt proteinuria (urinary protein/creatinine ratio [uPCR] > 1 mg/mg Cr). To estimate intrarenal RAS activity we measured urinary excretion of angiotensinogen (uAGT) and renin (uRenin) in patients with DN (n = 38) and NDN (n = 78)., Results: Both natural logarithms of uAGT/urinary creatinine (ln[uAGT/uCr]) and uRenin (ln[uRenin/uCr]) levels were significantly higher in patients with DN compared with those with NDN (ln[uAGT/uCr]: 4.16 ± 1.13 in DN vs. 3.52 ± 1.21 in NDN, P = 0.007; ln[uRenin/uCr]: 5.66 ± 1.60 in DN vs. 4.29 ± 1.48 in NDN, P < 0.001), when estimated glomerular filtration rate (eGFR) and uPCR showed no significant difference between the two groups. In a subgroup analysis, according to amount of proteinuria, both uAGT and uRenin were higher in DN in patients with subnephrotic-range proteinuria (uPCR < 3.5 mg/mg Cr). However, in patients with nephrotic-range proteinuria (uPCR ≥ 3.5 mg/mg Cr), only uRenin was higher in DN compared to NDN. In a multiple regression analysis, diabetes showed independent association with uRenin., Conclusion: Consistently elevated uRenin in DN, regardless of the amount of proteinuria, indicates that intrarenal RAS activity may be higher in DN compared to NDN in patients with overt proteinuria., (© 2014 Asian Pacific Society of Nephrology.)

Urinary angiotensinogen (AGT) and renin have been reported to reflect the intrarenal renin-angiotensin system (RAS) activity. However, the adequacy and clinical significance of these markers have not been evaluated in overtly proteinuric patients. In patients with biopsy-proven glomerulonephritis, plasma and urinary AGT and renin were analyzed. A cohort of 75 patients treated with RAS inhibitors was followed for 1 year. Among the 207 patients, 105 had subnephrotic and 102 had nephrotic-range proteinuria. Mean age, estimated glomerular filtration rate (eGFR), and urinary protein-to-creatinine ratio (P/Cr) of all patients were 48 years, 79.7 mL/min/1.73 m(2), and 5.66 mg/mg, respectively. Both natural logarithm of urinary AGT/creatinine (ln [urinary AGT/Cr]) and ln (urinary renin/Cr) showed positive correlations with urinary P/Cr. There was a positive correlation between ln (urinary AGT/Cr) and ln (urinary renin/Cr). Ln (urinary renin/Cr) was not affected by ln (plasma renin) regardless of the degree of proteinuria. The treatment response to RAS inhibitors was greatest in patients with high urinary AGT and renin. However, the predictive value of those parameters was no longer present when the values were adjusted by the degree of proteinuria. Ln (urinary renin/Cr) and initial eGFR were independently associated with the changes in renal function for 1 year. Ln (urinary AGT/Cr) was associated with persistent overt proteinuria after 1 year. Our study suggests that urinary renin may be a better marker in heavy proteinuria, and the treatment response to RAS inhibitors may be enhanced in patients with high urinary renin and AGT. Further studies will be necessary to explore the value of urinary AGT and renin., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Urinary angiotensinogen (AGT) was reported as a marker of renal injury in chronic kidney disease patients. However, the main source of urinary AGT is unknown in proteinuric patients because the disrupted filtration barrier might cause AGT filtration. We investigated the origin and the clinical importance of urinary AGT in proteinuric IgA nephropathy (IgAN) patients., Methods: In patients with biopsy-proven IgAN, urinary and plasma AGT was measured using a sandwich ELISA and compared with intrarenal AGT expression. The patients were followed up for 3 years., Results: Natural logarithm of the urinary AGT/creatinine (ln (urinary AGT/Cr)) was positively correlated with intrarenal expression of AGT (ln (urinary AGT/Cr) versus AGT/β-actin, r = 0.620, P < 0.0001; ln (urinary AGT/Cr) versus AGT density, r = 0.452, P = 0.007). Ln (urinary AGT/Cr) showed a positive correlation with urinary protein/creatinine ratio (PCR) but a negative correlation with estimated glomerular filtration rate (eGFR). Regression analyses showed that ln (urinary AGT/Cr) was a significant determinant of urinary PCR and eGFR 3 years after biopsy., Conclusions: Urinary AGT reflects intrarenal AGT expression and correlates with the extent of proteinuria and renal function. Our study indicates the intrarenal compartment as the main source of urinary AGT, suggesting its clinical implication as an important biomarker in proteinuric IgAN patients.

Objectives: Many chronic kidney disease (CKD) patients have persistent overt proteinuria despite angiotensin receptor blocker (ARB) treatment. This study investigated whether the initial difference in intrarenal renin-angiotensin system activity measured with urinary angiotensinogen would affect the antiproteinuric effects of ARB., Methods: Between September 2005 and September 2008, in 50 non-diabetic proteinuric CKD patients not taking renin-angiotensin system inhibitors, the urinary protein/creatinine ratio (P/Cr), angiotensinogen/creatinine ratio (AGT/Cr), plasma renin and aldosterone were measured before starting valsartan, and were followed for 18 months., Results: Patients were divided into three groups according to their initial urinary AGT/Cr. The urinary P/Cr was lower in the low angiotensinogen group, but similar in the high and extremely high angiotensinogen groups (1.3±0.38 vs 2.0±0.92 vs 2.2±0.78). In all groups, the urinary P/Cr was decreased most for the first 6 months. The urinary P/Cr reduction at 6 months was greatest in the high angiotensinogen group (-24.2% vs -46.2% vs -16.4%). The urinary AGT/Cr was decreased most in the high angiotensinogen group. Renal functional deterioration was attenuated in the high angiotensinogen group compared with the extremely high angiotensinogen group., Conclusions: The antiproteinuric effects of ARB were different according to the initial urinary angiotensinogen levels. These results suggest the potential value of the initial urinary AGT/Cr for predicting the therapeutic effect of ARB in proteinuric non-diabetic CKD patients.

Purpose: Activation of the rennin-angiotensin system (RAS) is thought to contribute to hypertension and proteinuria, and eventually to the progression of chronic kidney disease (CKD). Recent evidence suggests that urinary angiotensinogen (UAGT) excretion reflects activation of the intrarenal RAS. This study was performed to determine the effect of losartan on proteinuria and UAGT excretion in non-diabetic patients with CKD with non-nephrotic-range proteinuria., Study Design: Thirty-two patients with non-nephrotic-range proteinuria (0.045-0.23 g/mmol creatinine) and normal renal function between April 2005 and April 2006 were randomised to a losartan (n=17) or a control (n=15) group. Patients in the losartan group received losartan 50 mg/day, and the doses were titrated up to 100 mg/day after 6 weeks. Serum and urinary angiotensinogen concentrations were measured by sandwich ELISA. The primary end point was the percentage change in proteinuria. The secondary end points were changes in estimated glomerular filtration rate and UAGT excretion. The follow-up period was 24 months., Results: Baseline characteristics in the two groups were similar. After 24 months, losartan had reduced urinary protein excretion by 43% (from mean±SD 0.13±0.04 to 0.073±0.03 g/mmol, p<0.0001), but proteinuria had not changed in the control group. The percentage change in mean arterial pressure did not differ between the groups. Losartan decreased logarithmically converted UAGT excretion (from 1.58±0.47 to 1.00±0.52, p=0.001). Estimated glomerular filtration rate decreased significantly only in the control group., Conclusion: Losartan significantly decreased proteinuria and UAGT excretion, and preserved renal function in non-diabetic patients with CKD.

Aim: The renoprotective effects of angiotensin receptor blockers vary considerably among individuals. We investigated the renoprotective effects of valsartan according to polymorphisms of the renin-angiotensin system and transforming growth factor-b1 (TGFB1) genes in patients with chronic non-diabetic proteinuric nephropathies., Methods: Two hundred and thirty-nine non-diabetic patients with proteinuria of at least 1 g/day were enrolled. Patients received 80 g of valsartan daily, followed by 160 mg/day after 6 weeks. The follow-up period was 18 months. The status of the angiotensin-converting enzyme (ACE) insertion/deletion, angiotensinogen (AGT) M235T, type 1 angiotensin II receptor (ATR1) A1166C, and TGFB1 C509 and T869C polymorphisms was determined in 162 patients., Results: Valsartan treatment caused a significant reduction in proteinuria from baseline throughout the study in patients with each genotype of the ACE, AGT and TGFB1 genes. However, patients with the ATR1 AC genotype had no significant reduction in proteinuria from baseline throughout the study course. The median reductions in proteinuria after 6 months were 45.7% and 10.8% in the patients with the ATR1 AA and AC genotypes, respectively (P = 0.034). The annual change in the estimated glomerular filtration rate did not differ significantly among the genotypes for each gene. On multiple regression analysis, the change in proteinuria after 6 months of treatment was independently associated with the ATR1 genotype and the change in blood pressure (P = 0.005 and 0.019, respectively)., Conclusion: Valsartan treatment significantly reduced the blood pressure and urinary protein excretion of patients with chronic non-diabetic proteinuric nephropathies. Interindividual differences in the anti-proteinuric effect of valsartan may be related partly to the ATR1 A1166C polymorphism., (© 2011 The Authors. Nephrology © 2011 Asian Pacific Society of Nephrology.)

It is generally accepted that one-year post-transplant proteinuria over 0.5 gm per day has a negative impact on renal graft survival. In this study, the effects of minimal proteinuria less than 0.5 g/day were analyzed in 272 renal recipients who had survived for one year with a functioning graft. Recipients were classified by one-year post-transplant proteinuria: no proteinuria group (<0.2 g/day), minimal proteinuria group (0.2-0.5 g/day), and overt proteinuria group (>or=0.5 g/day). Recipients were followed up for 87.1+/-21 months after transplantation and 38 (13.9%) lost their graft during follow-up. Fifteen percent of patients had minimal proteinuria and 7.8% had overt proteinuria. Five-year graft survival in the minimal proteinuria group was 83.0%, and that in the overt proteinuria group was 70%, in contrast to 97.1% in the no proteinuria group (p=0.01 for trend). In a multivariate analysis, the minimal proteinuria group (relative risk [RR], 4.90; 95% confidence interval [CI], 2.09-11.46) and the overt proteinuria group (RR, 8.75; 95% CI, 3.29-23.29) had higher risks of graft failure than the no proteinuria group. Even minimal proteinuria at one year after transplantation was strongly associated with poor graft outcome. Therefore, it appears logical to consider a low level of proteinuria as a risk factor for graft survival in renal recipients.

Fanconi syndrome (FS) is a rare condition that is characterized by defects in the proximal tubular function. A 48-year-old woman was admitted for evaluation of proteinuria. The patient showed normal anion gap acidosis, normoglycemic glycosuria, hypophosphatemia, and hypouricemia. Thus, her condition was compatible with FS. The M peak was found behind the beta globulin region in urine protein electrophoresis. Upon bone marrow examination, we found that 24% of cells were CD138+ plasma cells with kappa restriction. From a kidney biopsy, we found crystalline inclusions within proximal tubular epithelial cells. Thereafter, she was diagnosed with FS accompanied by multiple myeloma. The patient received chemotherapy and autologous stem cell transplantation, and obtained very good partial hematologic response. However, proximal tubular dysfunction was persistent until 1 year after autologous stem cell transplantation. In short, we report a case of FS accompanied by multiple myeloma, demonstrating crystalline inclusion in proximal tubular cells on kidney biopsy. [ABSTRACT FROM AUTHOR]

Abstract: Idiopathic membranous nephropathy is a common cause of nephrotic syndrome, and has been reported as a cause of idiopathic primary glomerulonephropathy in up to 90% of patients. However, the treatment options remain controversial. We report two cases of idiopathic membranous nephropathy that were treated with rituximab. A 54-year-old man and a 64-year old man were admitted for rituximab therapy. They had previously been treated with combinations of immunosuppressive agents including cyclophosphamide, cyclosporine, mycophenolate, and steroids. However, the patients' heavy proteinuria was not resolved. Both patients received rituximab therapy, 2 weeks apart. After several months of follow-up and a second round of rituximab treatment for each patient, their proteinuria decreased and partial remission of disease was achieved in both patients. [Copyright &y& Elsevier]

Background. Nephrin is a recently identified protein, which is synthesized in the podocytes and localized in the slit diaphragm area. Nephrin is a cell adhesion molecule of the immunoglobulin superfamily, and presumably is a part of the zipper‐like structure of the slit membrane. As the mutation of the gene coding nephrin induces congenital nephrotic syndrome of Finnish type, which is a prototype of nephrotic syndrome, it has been suggested that nephrin also plays a role in acquired proteinuric kidney disease. [ABSTRACT FROM PUBLISHER]