Higher Levels Of Proteinuria Research Articles

Respiratory Syncytial Virus Aggravates Renal Injury through Cytokines and Direct Renal Injury.

The purpose of this study was to investigate the relationship between renal injury and reinfection that is caused by respiratory syncytial virus (RSV) and to analyze the mechanism of renal injury. Rats were repeatedly infected with RSV on days 4, 8, 14, and 28, then sacrificed and examined on day 56 after the primary infection. Renal injury was examined by transmission electron microscopy and histopathology. The F protein of RSV was detected in the renal tissue by indirect immunofluorescence. Proteinuria and urinary glycosaminoglycans (GAGs), serum levels of albumin, urea nitrogen, and creatinine, secretion of cytokines, T lymphocyte population and subsets, and dendritic cell (DC) activation state were examined. The results showed that renal injury was more serious in the reinfection group than in the primary infection group. At a higher infection dose, 6 × 106 PFU, the renal injury was more severe, accompanied by higher levels of proteinuria and urinary GAGs excretion, and lower levels of serum albumin. Podocyte foot effacement was more extensive, and hyperplasia of mesangial cells and proliferation of mesangial matrix were observed. The maturation state of DCs was specific, compared with the primary infection. There was also a decrease in the ratio of CD4+ to CD8+ T lymphocytes, due to an increase in the percentage of CD8+ T lymphocytes and a decrease in the percentage of CD4+ T lymphocytes, and a dramatic increase in the levels of IL-6 and IL-17. In terms of the different reinfection times, the day 14 reinfection group yielded the most serious renal injury and the most significant change in immune function. RSV F protein was still expressed in the glomeruli 56 days after RSV infection. Altogether, these results reveal that RSV infection could aggravate renal injury, which might be due to direct renal injury caused by RSV and the inflammatory lesions caused by the anti-virus response induced by RSV.

Effect of Proteinuria and Glomerular Filtration Rate on Renal Outcome in Patients with Biopsy-Proven Benign Nephrosclerosis.

BackgroundReduced estimated glomerular filtration rate (eGFR) and proteinuria are risk factors for end-stage renal disease (ESRD), of which benign nephrosclerosis is a common cause. However, few biopsy-based studies have assessed these associations.MethodsWe performed retrospective cohort study of 182 Japanese patients who underwent renal biopsy from June 1985 through March 2014 and who were diagnosed with benign nephrosclerosis. Competing risk regression analyses were used to investigate the effect of eGFR and proteinuria levels at the time of renal biopsy on the risk for renal events (ESRD or a 50% decline in eGFR from baseline).ResultsDuring a median 5.8-year follow-up, 63 (34.6%) patients experienced renal events. The incidence of renal events increased with lower baseline eGFR and greater baseline proteinuria levels. After adjustment for baseline covariates, lower eGFR levels (subhazard ratios [SHRs], 1.30; 95% confidence interval [CI], 1.01–1.67, per 10 mL/min/1.73 m2) and higher proteinuria levels (SHR, 1.52; 95% CI, 1.23–1.87, per 1.0 g/day) at the time of renal biopsy were associated independently with higher risk for renal events. Lower levels of serum albumin (SHR, 2.07; 95% CI, 1.20–3.55 per 1.0 g/dL) were also associated with renal events. Patients with both eGFR <30 mL/min/1.73 m2 and proteinuria ≥0.5 g/day had a 26.7-fold higher risk (95% CI, 3.97–179.4) of renal events than patients with both eGFR ≥60 mL/min/1.73 m2 and proteinuria <0.5 g/day.ConclusionsReduced eGFR and increased proteinuria as well as lower serum albumin at the time of renal biopsy are independent risk factors for renal events among patients with biopsy-proven benign nephrosclerosis.

Prognostic Significance of Creeping Proteinuria in the First Year After Transplantation.

Proteinuria changes have a prognostic significance in proteinuric nephropathies. Proteinuria has been related to kidney transplant outcomes, but there are no information about the impact of increasing proteinuria during the first year on long-term graft and patient survival. Retrospective cohort study of 591 kidney transplants to analyze the effect on long-term prognosis of: proteinuria at 3 (n = 591) and 12 (n = 583) months (no proteinuria: 150-299 mg/24 hours, 300-999 mg/24 hours, and ≥1 g/24 hours), and changes in proteinuria during the first year in such patients with proteinuria at 3 months (reduction ≥50% of proteinuria from 3 to 12 months, variation <50%, and increase ≥50% or "creeping proteinuria") (n = 283). Higher levels of proteinuria, at both 3 and 12 months, were progressively related to lower graft survival (P < 0.0001). Proteinuria at 12 months was related to mortality (P = 0.026). Creeping proteinuria, which was present in 35 patients (12.4%), was related to graft failure (P < 0.0001) and mortality (P = 0.030), even at lower levels of proteinuria at 3 months. De novo HLA antibody development was the only factor related to creeping proteinuria (hazard ratio, 2.946; 95% confidence interval, 1.158-7.491; P = 0.023). Creeping proteinuria during the first year was associated with long-term graft failure and mortality and could be considered as a surrogate of kidney disease progression in the renal transplant population, as it is in proteinuric nephropathies. It could also be viewed as an expression of immunological damage.

Long-term outcome of IgA nephropathy with minimal change disease: a comparison between patients with and without minimal change disease

The clinicopathological characteristics, treatment response and long-term outcome of immunoglobulin (Ig)A nephropathy with minimal change disease (MCD-IgAN) are not well defined. Patients with biopsy-proven MCD-IgAN from the Jinling Hospital IgA nephropathy Registry were systematically reviewed and compared with those with IgA nephropathy without minimal change disease (Non-MCD-IgAN). We compared data of 247 MCD-IgAN patients and 1,121 Non-MCD-IgAN patients. Compared to Non-MCD-IgAN, MCD-IgAN patients were younger,with male predominance, had higher levels of proteinuria, total cholesterol and estimated glomerular filtration rate (eGFR), lower incidence of hypertension and microhematuria, lower level of serum creatinine, and had less severe glomerular, tubulointerstitial and vascular lesions in renal pathology. In the Non-MCD-IgAN group, 157 patients (14.0%) reached the renal endpoint and 103 patients (9.2%) entered end-stage renal disease (ESRD). The 5-,10-, 15- and 20-year cumulative renal survival rates from ESRD, calculated by Kaplan-Meier method, were 95.0, 83.0, 72.9 and 65.4%, respectively. In the MCD-IgAN group, no patients entered ESRD and only 4 (1.6%) reached the renal endpoint. Patients with MCD-IgAN had a significantly better renal outcome than Non-MCD-IgAN (p<0.01). At multivariate Cox analysis, proteinuria>1.0g/day, hypertension, eGFR<60ml/min/1.73m(2), hypoproteinemia and hyperuricemia were independent risk factors of renal survival for Non-MCD-IgAN patients [hazard ratio (HR) 3.43, p<0.001; HR 1.65, p<0.05; HR 2.61, p<0.001; HR 2.40, p<0.001; HR 2.27, p<0.001, respectively), but not for patients with MCD-IgAN. The long-term outcome of patients with MCD-IgAN is significantly better than that of patients with Non-MCD-IgAN.

TLR2–MyD88–NF-κB pathway is involved in tubulointerstitial inflammation caused by proteinuria

Proteinuria is an important risk factor for chronic kidney diseases (CKD). Several studies have suggested that proteinuria initiates tubulointerstitial inflammation, while the mechanisms have not been fully understood. In this study, we hypothesized whether the activation of the TLR2–MyD88–NF-κB pathway is involved in tubulointerstitial inflammation induced by proteinuria. We observed expression of TLR2, MyD88, NF-κB, as well as TNF-α and IL-6 detected by immunohistostaining, Western blotting and real-time PCR in albumin-overloaded (AO) nephropathy rats. In vitro, we observed these markers in HK-2 cells stimulated by albumin. We used TLR2 siRNA or the NF-κB inhibitor BAY 11-7082 to observe the influence of TNF-α and IL-6 expression caused by albumin overload. Finally, we studied these markers in non-IgA mesangioproliferative glomerulonephritis (MsPGN) patients with different levels of proteinuria. It was demonstrated that expression of TLR2, MyD88 and NF-κB were significantly increased in AO rats and in non-IgA MsPGN patients with high levels of proteinuria, and TNF-α and IL-6 expressions were increased after NF-κB activation. Furthermore, TNF-α and IL-6 expression was positively correlated with the level of proteinuria. Albumin-overload induced TNF-α and IL-6 secretions by the TLR2–MyD88–NF-κB pathway activation, which could be attenuated by the TLR2 siRNA or BAY 11-7082 in HK-2 cells. In summary, we demonstrated that proteinuria may exhibit an endogenous danger-associated molecular pattern (DAMP) that induces tubulointerstitial inflammation via the TLR2–MyD88–NF-κB pathway activation.

Reversible posterior encephalopathy syndrome in children with nephrotic syndrome

To investigate the clinical features and prognoses of children who develop reversible posterior encephalopathy syndrome (RPES) during treatment for nephrotic syndrome (NS). The clinicoradiological characteristics and prognoses of 51 patients with NS, including 21 with RPES and 30 without, were analyzed. Compared with the controls, the RPES patients exhibited a higher rate of tacrolimus (P = 0.01) and cyclosporine (P = 0.02) treatment; higher-dose prednisolone (P = 0.01) treatment; higher systolic blood pressure (P = 0.04), serum cholesterol (P = 0.03), and proteinuria (P < 0.01); and lower serum albumin levels (P = 0.03). Hypertension was present in 85.7% of RPES patients. The clinical manifestations of RPES included an altered mental status, seizures, headaches, nausea and vomiting, and visual impairment. Electroencephalography findings included slow waves and focal sharp or/and spiked waves; magnetic resonance imaging showed lesions localized in the occipital, parietal, frontal, temporal lobes and the cerebellum and brainstem; and magnetic resonance angiography revealed vertebral artery narrowing. All RPES patients recovered completely with timely and appropriate therapy. Hypertension, calcineurin inhibitor and high-dose steroid treatments, high serum cholesterol and proteinuria levels, and low serum albumin levels can predispose children with NS to RPES, although both the clinical and imaging outcomes are satisfactory.

Glomerulomegaly in lupus nephritis: a prognostic marker for renal outcomes.

Glomerulomegaly refers to the abnormal enlargement of glomeruli and is associated with an increased risk of progressive chronic kidney disease (CKD). However, it has rarely been investigated in lupus nephritis (LN). We therefore assessed glomerulomegaly as a prognostic factor for renal pathology. Patients with class III or IV LN were retrospectively recruited and divided into two groups according to complete renal response (CR) at 3 years after the initiation of induction therapy. Baseline clinical and renal pathological findings were compared to identify prognostic factors, and patients were followed for up to 10 years to assess long-term renal outcomes. Nineteen patients with and 19 without CR on 3-year follow-up were analyzed. Long-term disease duration and high levels of proteinuria were frequently observed in patients without CR (P = 0.03 and P = 0.01, respectively) at baseline compared to those with CR. On renal pathological analysis, a significantly higher proportion of patients without CR had enlarged glomeruli than those with CR (P = 0.03) in analysis of segmentally or minimally affected glomeruli. On 10-year follow-up, a higher proportion of patients without enlarged glomeruli maintained CR compared to those with enlarged glomeruli (P = 0.004). Further, glomerular area and disease duration were significantly correlated (P = 0.04). Enlarged segmentally or minimally affected glomeruli at diagnosis of LN might predict a worse renal prognosis at 3 years after induction therapy. Mechanical glomerular injury might influence clinical outcomes.

Haematuria increases progression of advanced proteinuric kidney disease.

BackgroundHaematuria has been traditionally considered as a benign hallmark of some glomerular diseases; however new studies show that haematuria may decrease renal function.ObjectiveTo determine the influence of haematuria on the rate of chronic kidney disease (CKD) progression in 71 proteinuric patients with advanced CKD (baseline eGFR <30 mL/min) during 12 months of follow-up.ResultsThe mean rate of decline in eGFR was higher in patients with both haematuria and proteinuria (haemoproteinuria, HP, n=31) than in patients with proteinuria alone (P patients, n=40) (-3.8±8.9 vs 0.9±9.5 mL/min/1.73m2/year, p<0.05, respectively). The deleterious effect of haematuria on rate of decline in eGFR was observed in patients <65 years (-6.8±9.9 (HP) vs. 0.1±11.7 (P) mL/min/1.73m2/year, p<0.05), but not in patients >65 years (-1.2±6.8 (HP) vs. 1.5±7.7 (P) mL/min/1.73m2/year). Furthermore, the harmful effect of haematuria on eGFR slope was found patients with proteinuria >0.5 g/24 h (-5.8±6.4 (HP) vs. -1.37± 7.9 (P) mL/min/1.73m2/year, p<0.05), whereas no significant differences were found in patients with proteinuria < 0.5 g/24 h (-0.62±7.4 (HP) vs. 3.4±11.1 (P) mL/min/1.73m2/year). Multivariate analysis reported that presence of haematuria was significantly and independently associated with eGFR deterioration after adjusting for traditional risk factors, including age, serum phosphate, mean proteinuria and mean serum PTH (β=-4.316, p=0.025).ConclusionsThe presence of haematuria is closely associated with a faster decrease in renal function in advanced proteinuric CKD patients, especially in younger CKD patients with high proteinuria levels; therefore this high risk subgroup of patients would benefit of intensive medical surveillance and treatment.

Clinical and perinatal outcomes in eclamptic women with posterior reversible encephalopathy syndrome.

To compare the clinical and perinatal outcomes in eclamptic women with and without posterior reversible encephalopathy syndrome (PRES). This single-center, retrospective, cohort study was conducted between 2008 and 2013. The clinical and perinatal outcomes of eclamptic patients were obtained from hospital records. Magnetic resonance imaging was used for the diagnosis of PRES. Eighty-one eclamptic women were divided into two groups: 45 and 36 patients were included in the PRES and non-PRES groups, respectively. In the PRES group, headache and visual impairment together (60.0%) were the most common presenting symptoms. In the non-PRES group, only headache was the most common (50%) presenting symptom. Occipital and parietal lobes were the most frequently affected areas in the PRES group. Women in the PRES group had a higher body mass index value (p=0.005), longer hospitalization time (p=0.001), and higher level of proteinuria (p=0.012) than those in the non-PRES group. Women in the non-PRES group had higher Apgar scores (p=0.002) than those in the PRES group. This study indicates that PRES manifests predominantly with headache and visual impairment together. Adverse neonatal outcomes are also common in these patients.

Pauci-immune crescentic glomerulonephritis: A series of 21 cases

Background: Pauci-immune crescentic glomerulonephritis is the most common cause of crescentic glomerulonephritis (CrGN). Patients usually present with rapidly progressive glomerulonephritis (RPGN) with hematuria, proteinuria, and elevated serum creatinine levels. The characteristic feature of pauci-immune CrGN is focal necrotizing CrGN associated with little or no glomerular staining for immunoglobulin (Ig) by immunofluorescence microscopic examination. Most patients (80-85%) with pauci-immune CrGN, including the patients with and without systemic vasculitis, have antineutrophil cytoplasmic autoantibodies (ANCAs). Aims and Objectives: To study and compare the histological and laboratory features of ANCA-positive and ANCA-negative pauci-immune CrGN. Materials and Methods: Patients who were diagnosed with pauci-immune CrGN from January 2012 to May 2015, at BABINA Diagnostics, were included in this retrospective study. The terms pauci-immune and crescentic glomerulonephritis were defined according to standard guidelines. The demographic and laboratory data were extracted from the Laboratory Information System (LIS) for analysis. ANCA tests were performed by both indirect immunofluorescence (IIF) assay (EUROIMMUN, Lubeck, Germany) and antigen-specific enzyme-linked immunosorbent assay (ELISA) (ORGENTEC Diagnostika GmbH, Germany). Renal specimens were evaluated using direct immunofluorescence (for Ig and complement components) and light microscopy using routine and special stains. Results: Four (19%) out of the 21 cases of pauci-immune CrGN were ANCA negative. Acute features on histology were seen more than chronic features than ANCA-negative cases. Conclusion: Among the patients with pauci-immune CrGN, ANCA-negative patients were not rare. Compared with ANCA-positive patients, ANCA-negative patients had a lower percentage of normal glomeruli, more of chronic features, and a higher level of proteinuria.

Factors Associated with Uncontrolled Hypertension among Renal Transplant Recipients Attending Nephrology Clinics in Nairobi, Kenya.

Objective. To determine the factors associated with poor blood pressure control among renal transplant recipients in a resource-limited setting. Methods. A cross-sectional study was carried out on renal transplant recipients at the Kenyatta National Hospital. Sociodemographic details, blood pressure, urine albumin : creatinine ratio, and adherence using the MMAS-8 questionnaire were noted. Independent factors associated with uncontrolled hypertension were determined using logistic regression analysis. Results. 85 subjects were evaluated. Mean age was 42.4 (SD ± 12.2) years, with a male : female ratio of 1.9 : 1. Fifty-five patients (64.7%) had uncontrolled hypertension (BP ≥ 130/80 mmHg). On univariate analysis, male sex (OR 3.7, 95% CI 1.4–9.5, p = 0.006), higher levels of proteinuria (p = 0.042), and nonadherence to antihypertensives (OR 18, 95% CI 5.2–65.7, p < 0.001) were associated with uncontrolled hypertension. On logistic regression analysis, male sex (adjusted OR 4.6, 95% CI 1.1–19.0, p = 0.034) and nonadherence (adjusted OR 33.8, 95% CI 8.6–73.0, p < 0.001) were independently associated with uncontrolled hypertension. Conclusion. Factors associated with poor blood pressure control in this cohort were male sex and nonadherence to antihypertensives. Emphasis on adherence to antihypertensive therapy must be pursued within this population.

B cell abnormalities in a mouse model of SLE

Event Abstract Back to Event B cell abnormalities in a mouse model of SLE Camila Fuentes1, Natalia Crisostomo1, María A. Gleisner2, 3, Mario Rosemblatt1, 4 and Maria R. Bono1* 1 Laboratorio de Inmunología, Facultad de Ciencias, Universidad de Chile, Chile 2 Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Chile 3 Instituto Milenio de Inmunología e Inmunoterapia, Universidad de Chile, Chile 4 Fundación Ciencia & Vida, Chile Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology characterized by the activation of autoreactive T and B cells, autoantibody production and immune complex deposition causing damage in multiple tissues. B cells play a critical role in the development of SLE. Besides the production of auto-antibodies, it has been described that B cells have the ability to produce cytokines and present antigens, which allows them to have different roles during the immune response. Using a spontaneous autoimmune disease setting, (NZWxNZB) F1 (BWF1) mice, that develops SLE at the age of 6 months, characterized by high proteinuria levels and serum autoantibody titers, we analyzed different B cell subpopulations such as regulatory and memory populations through flow cytometry (FACS) using specific B cell markers. Important differences were seen on the regulatory B cells populations, plasma cells and B10 cells which were increased on spleen of BWF1 aged autoimmune mice. We also studied the effect of dendritic cells (DCs) in vivo over B cells and their participation in the development of the disease. Two doses of DCs from BWF1 aged autoimmune mice were transferred onto BWF1 young pre-autoimmune mice. Two months after the adoptive transfer of DCs, mice were sacrificed and B cells were studied by FACS analysis. Our results showed that the adoptive transfer of DCs from BWF1 aged autoimmune mice into BWF1 young pre-autoimmune mice promoted an accelerated and exacerbated humoral response comparable to that seen on the normal development of SLE. Thus, treatment with DCs from BWF1 aged autoimmune mice caused significant changes in the phenotype and distribution of B cells from BWF1 young pre-autoimmune mice, similar to what we see on BWF1 aged autoimmune mice, indicating that the interaction between B cells and DCs maybe determining in the development of the disease. Acknowledgements Funded by FONDECYT 1100557, PFB-16. Keywords: Lupus Erythematosus, Systemic, B cells, Dendritic Cells, Autoimmune Diseases, Autoantibodies Conference: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología, Medellin, Colombia, 13 Oct - 16 Oct, 2015. Presentation Type: Poster Presentation Topic: Autoimmunity Citation: Fuentes C, Crisostomo N, Gleisner MA, Rosemblatt M and Bono MR (2015). B cell abnormalities in a mouse model of SLE. Front. Immunol. Conference Abstract: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología. doi: 10.3389/conf.fimmu.2015.05.00207 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 14 Apr 2015; Published Online: 14 Sep 2015. * Correspondence: Prof. Maria R Bono, Laboratorio de Inmunología, Facultad de Ciencias, Universidad de Chile, Santiago, Chile, mrbono@uchile.cl Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Camila Fuentes Natalia Crisostomo María A Gleisner Mario Rosemblatt Maria R Bono Google Camila Fuentes Natalia Crisostomo María A Gleisner Mario Rosemblatt Maria R Bono Google Scholar Camila Fuentes Natalia Crisostomo María A Gleisner Mario Rosemblatt Maria R Bono PubMed Camila Fuentes Natalia Crisostomo María A Gleisner Mario Rosemblatt Maria R Bono Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Association between ratio of measured extracellular volume to expected body fluid volume and renal outcomes in patients with chronic kidney disease: a retrospective single-center cohort study.

BackgroundExcess extracellular volume is a major clinical problem in patients with chronic kidney disease (CKD). However, whether the extracellular volume status is associated with disease progression is unclear. We investigated the association between the extracellular volume status and renal outcomes.MethodsWe performed a retrospective cohort study of 149 patients with CKD who underwent bioelectrical impedance analysis (BIA) from 2005 to 2009. Patients were categorized according to tertiles of extracellular volume status. The extracellular volume status was assessed by examining the ratio of extracellular water measured by BIA (ECWBIA) to the total body water calculated using the Watson formula (TBWWatson). The main outcomes were adverse renal outcomes as defined by a decline of ≥50% from the baseline glomerular filtration rate or initiation of renal replacement therapy.ResultsA higher %ECWBIA/TBWWatson ratio tended to be associated with older age, male sex, diabetes mellitus, resistant hypertension, lower renal function, lower serum albumin levels, higher proteinuria levels, and a higher frequency of furosemide use. In the multivariate analysis, proteinuria remained independently associated with the %ECWBIA/TBWWatson ratio. Both the intracellular and extracellular water volumes decreased with age (correlation between ICW and age, r = -0.30, P < 0.001; correlation between ECW and age, r = -0.17, P = 0.03). Consequently, the %ECWBIA in the body fluid composition increased with age. During a median follow-up of 4.9 years, patients in the highest tertile of the %ECWBIA/TBWWatson ratio were at greater risk of adverse renal outcomes (16.6 per 100.0 patient years) than were those in the lowest tertile (8.1 per 100.0 patient years) or second tertile (5.6 per 100.0 patient years) (log-rank P = 0.005). After adjustment for covariates, the %ECWBIA/TBWWatson ratio was significantly associated with adverse renal outcomes (hazard ratio, 1.21; 95 % confidence interval, 1.10–1.34; P < 0.001).ConclusionsThe ECWBIA/TBWWatson ratio was independently associated with adverse renal outcomes. Proteinuria was independently associated with the extracellular volume status. The balance between ICW and ECW changes with age in that the percentage of ECW content in the body fluid composition increases. Elderly patients with CKD may thus be susceptible to volume overload.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2369-15-189) contains supplementary material, which is available to authorized users.

Characteristics of IgA nephropathy in advanced-age patients.

The susceptible age for IgA nephropathy (IgAN) is <30 years. However, IgAN sometimes develops in people aged >60 years, and its characteristics remain unknown. We divided 600 IgAN patients into three groups: advanced-age group (AAG, n=31, ≥60 years); middle-aged group (MAG, n=162, 40-59 years); and young-aged group (YAG, n=407, 20-39 years). We analyzed clinical and histological background, renal outcome, and risk of progression. In the AAG, mean arterial pressure (MAP) and the number of hypertensive patients were significantly higher than in the YAG. Total protein, serum albumin, and estimated glomerular filtration rate were significantly lower, and blood urea nitrogen, proteinuria, and N-acetyl-β-D-glucosaminidase were significantly higher in the AAG than in MAG and YAG. In histological findings, interstitial fibrosis/tubular atrophy by Oxford classification and arteriosclerosis were more severe in the AAG than the in YAG. Renal survival rate analyzed by Kaplan-Meier method was significantly lower in the AAG (22.9%/19 years in the AAG vs. 69.2 and 84.9%/20 years in the MAG and YAG, p<0.0001). The patients who progressed to end-stage renal disease (ESRD) in the AAG had higher MAP and more severe proteinuria compared with the patients who did not progress to ESRD in the AAG. The characteristics of IgAN in advanced-age were lower renal function, high levels of proteinuria, severe interstitial change, and arteriolosclerosis caused by glomerulopathy and concomitant diseases, such as hypertension, dyslipidemia, and hyperuricemia. Prognosis was poor, and >70% developed ESRD within 20 years.

Elevated levels of protein in urine in adulthood after exposure to the Chinese famine of 1959-61 during gestation and the early postnatal period.

Animal models have suggested that undernutrition during gestation and the early postnatal period may adversely affect kidney development and compromise renal function. As a natural experiment, famines provide an opportunity to test such potential effects in humans. We assessed whether exposure to the Chinese famine of 1959-1961 during gestation and early postnatal life was associated with the levels of proteinuria among female adults three decades after exposure to the famine. We measured famine intensity using the cohort size shrinkage index and we constructed a difference-in-difference model to compare the levels of proteinuria, measured with a dipstick test of random urine specimens, among Chinese women (n = 70 543) whose exposure status to the famine varied across birth cohorts (born before, during or after the famine) and counties of residence with different degrees of famine intensity. Famine exposure was associated with a greater risk [odds ratio (OR) = 1.54; 95% confidence interval (CI): 1.04, 2.28; P = 0.029) of having higher level of proteinuria among women born during the famine years (1959-61) compared with the unexposed post famine-born cohort (1964-65) in rural samples. No association was observed among urban samples. Results were robust to adjustment for covariates. Severe undernutrition during gestation and the early postnatal period may have long-term effects on levels of proteinuria in humans, but the effect sizes may be small.

Early Change in Proteinuria as a Surrogate End Point for Kidney Disease Progression: An Individual Patient Meta-analysis

It is controversial whether proteinuria is a valid surrogate end point for randomized trials in chronic kidney disease. Meta-analysis of individual patient-level data. Individual patient data for 9,008 patients from 32 randomized trials evaluating 5 intervention types. Randomized controlled trials of kidney disease progression until 2007 with measurements of proteinuria both at baseline and during the first year of follow-up, with at least 1 further year of follow-up for the clinical outcome. Early change in proteinuria. Doubling of serum creatinine level, end-stage renal disease, or death. Early decline in proteinuria was associated with lower risk of the clinical outcome (pooled HR, 0.74 per 50% reduction in proteinuria); this association was stronger at higher levels of baseline proteinuria. Pooled estimates for the proportion of treatment effect on the clinical outcome explained by early decline in proteinuria ranged from-7.0% (95%CI,-40.6% to 26.7%) to 43.9% (95%CI, 25.3% to 62.6%) across 5 intervention types. The direction of the pooled treatment effects on early change in proteinuria agreed with the direction of the treatment effect on the clinical outcome for all 5 intervention types, with the magnitudes of the pooled treatment effects on the 2 end points agreeing for 4 of the 5 intervention types. The pooled treatment effects on both end points were simultaneously stronger at higher levels of proteinuria. However, statistical power was insufficient to determine whether differences in treatment effects on the clinical outcome corresponded to differences in treatment effects on proteinuria between individual studies. Limited variety of interventions tested and low statistical power for many chronic kidney disease clinical trials. These results provide new evidence supporting the use of an early reduction in proteinuria as a surrogate end point, but do not provide sufficient evidence to establish its validity in all settings.

Basal proteinuria as a prognostic factor in patients with metastatic colorectal cancer treated with bevacizumab

BackgroundThe beneficial effects of bevacizumab, a widely used agent in metastatic colorectal cancer (mCRC), on clinical survival have been proven. This study investigated the correlation of the clinical benefits and prognosis with proteinuria and other parameters. MethodsThe study included mCRC patients receiving bevacizumab. Hypertension, 24-hour urine proteinuria, and other routine parameters were recorded at baseline and at certain intervals during treatment. ResultsThe study included 36 consecutive patients. The median progression-free survival (PFS) duration was 10.9±2.6months, and the median overall survival (OS) was 23±3.1months. The median PFS was 7.2months among patients with basal proteinuria above 114mg/day, whereas the median PFS was 12months among patients with an equal or lower level (P=0.010). Similarly, PFS was shorter in patients with high lactate dehydrogenase (LDH) or carcinoembryonic antigen (CEA) levels (LDH, P=0.022; CEA, P=0.014). Bevacizumab response's performance status was good (P=0.05) and was even better in patients with a single liver metastasis (P=0.034) or hypertension (P=0.034). ConclusionsWe demonstrated that high basal proteinuria, LDH, or CEA levels may be negative prognostic factors in mCRC patients receiving bevacizumab.

Time to Recovery from Proteinuria in Patients with Lupus Nephritis Receiving Standard Treatment

The recovery time from abnormal levels of proteinuria with standard treatment in longitudinal studies of patients with systemic lupus erythematosus has not been well described. We aimed (1) to determine the recovery time from proteinuria in patients with lupus nephritis (LN) receiving standard treatment, and (2) to determine whether the initial level of proteinuria predicts time to improvement. We studied all patients with LN recorded in the database from 1970 until 2011. Proteinuria was defined as ≥0.5 g/24 h. Patients were grouped as follows: group 1 having 0.5-0.9 g/day, group 2 having 1-1.9 g/day, and group 3 having ≥2 g/day. Recovery from proteinuria was defined as proteinuria<0.5 g/24 h. Time to recovery from proteinuria was studied with the Kaplan-Meier curves. Factors associated with proteinuria recovery were evaluated using proportional hazard models. Among the 212 patients studied, 52% recovered from proteinuria within 2 years and an additional 22% recovered within 5 years, for a total of 74%. The level of proteinuria at baseline visit predicted the time to improvement. Patients with a higher level of proteinuria at baseline needed a longer time to normalize their proteinuria. Male sex, hypocomplementemia, high level of proteinuria at diagnosis of LN, and disease duration>5 years at onset of LN each independently predicted late recovery of proteinuria and had an effect on the percentage of patients who recovered. The tempo of recovery from proteinuria in LN is slow and the level of proteinuria at baseline visit predicts the time to complete recovery.

Efficacy and safety of multi-target therapy using a combination of tacrolimus, mycophenolate mofetil and a steroid in patients with active lupus nephritis

Objectives. To examine the efficacy and safety of multi-target therapy using tacrolimus (TAC), mycophenolate mofetil (MMF) and a steroid as initial treatment for active lupus nephritis (LN).Methods. We conducted a retrospective analysis of the data of 16 consecutive patients who received the multi-target therapy for active Classes III–V LN at our department. We also compared the outcomes of the multi-target therapy with those of TAC therapy (TAC + steroid), a study of which we had conducted previously in 13 patients with active LN (TAC group).Results. All the patients treated with multi-target therapy achieved complete remission (CR) (mean, 4.6 ± 3.8 months; range, 1–15 months). The clinical profiles of the patients of the multi-target group were similar to those of the TAC group at baseline, except for a significantly higher level of proteinuria (4.6 ± 2.8 vs. 2.5 ± 2.1 g/gCr, p = 0.033) in the former. The CR rate at 6 months was significantly higher in the multi-target group as compared with that in the TAC group (81% vs. 38%, p = 0.018). Two cases of serious adverse events were associated with cytomegalovirus infection in the multi-target group, namely gastric ulcer and pancytopenia, both of which were successfully treated by antiviral therapy.Conclusions. Multi-target therapy was effective as initial treatment for active LN, with CR achieved early and in a high percentage of patients. Although this therapy was generally well tolerated, it is important to bear in mind the associated risk of cytomegalovirus infection.

Association between blood pressure and target organ damage in patients with chronic kidney disease and hypertension: results of the APrODiTe study

Blood pressure control is the most established practice for preventing the progression of chronic kidney disease. Evidence addressing blood pressure control status or nocturnal blood pressure dipping in Korean hypertensive patients with chronic kidney disease is scarce. We recruited 1317 hypertensive patients (chronic kidney disease stages 2-4, median age 58) from 21 centers in Korea. These patients underwent office and ambulatory blood pressure monitoring. High office and ambulatory blood pressure were defined as >140/90 mm Hg and >135/85 mm Hg (daytime)/ >120/70 mm Hg (nighttime), respectively. The blood pressure control status was as follows: true controlled (19%), white-coat (4.3%), masked (33.9%) and sustained uncontrolled (42.3%) hypertension. The dipping status was as follows: extreme-dipping (14.9%), dipping (33.3%), non-dipping (34.5%) and reverse-dipping (17.3%). Masked and sustained hypertension as well as non-dipping/reverse-dipping was more apparent in proportion to renal dysfunction and the extent of proteinuria. Ageing (58 years), male gender, obesity, diabetic nephropathy and proteinuria (>300 mg g(-1) Cr or dipstick proteinuria1+) were independently associated with sustained uncontrolled hypertension. Diabetic nephropathy, old age, a history of stable angina/heart failure, advanced renal dysfunction and higher proteinuria levels were also significantly associated with non-dipping and reverse-dipping. Half of Korean chronic kidney disease patients had uncontrolled blood pressure and a non-dipping nocturnal blood pressure pattern. Future studies are warranted to assess the predictive values of ambulatory blood pressure for cardiorenal events in Korean chronic kidney disease patients.