Unveiling the mechanisms of carboxylic acid esterification on acid zeolites for biomass-to-energy: A review of the catalytic process through experimental and computational studies.

In recent years, there has been significant interest from industrial and academic areas in the esterification of carboxylic acids catalyzed by acidic zeolites, as it represents a sustainable and economically viable approach to producing a wide range of high-value-added products. However, there is a lack of comprehensive reviews that address the intricate reaction mechanisms occurring at the catalyst interface at both the experimental and atomistic levels. Therefore, in this review, we provide an overview of the esterification reaction on acidic zeolites based on experimental and theoretical studies. The combination of infrared spectroscopy with atomistic calculations and experimental strategies using modulation excitation spectroscopy techniques combined with phase-sensitive detection is presented as an approach to detecting short-lived intermediates at the interface of zeolitic frameworks under realistic reaction conditions. To achieve this goal, this review has been divided into four sections: The first is a brief introduction highlighting the distinctive features of this review. The second addresses questions about the topology and activity of different zeolitic systems, since these properties are closely correlated in the esterification process. The third section deals with the mechanisms proposed in the literature. The fourth section presents advances in IR techniques and theoretical calculations that can be applied to gain new insights into reaction mechanisms. Finally, this review concludes with a subtle approach, highlighting the main aspects and perspectives of combining experimental and theoretical techniques to elucidate different reaction mechanisms in zeolitic systems.

AgDataBox-IoT - application development for agrometeorological stations in smart.

Currently, Brazil is one of the world's largest grain producers and exporters. Agriculture has already entered its 4.0 version (2017), also known as digital agriculture, when the industry has entered the 4.0 era (2011). This new paradigm uses Internet of Things (IoT) techniques, sensors installed in the field, network of interconnected sensors in the plot, drones for crop monitoring, multispectral cameras, storage and processing of data in Cloud Computing, and Big Data techniques to process the large volumes of generated data. One of the practical options for implementing precision agriculture is the segmentation of the plot into management zones, aiming at maximizing profits according to the productive potential of each zone, being economically viable even for small producers. Considering that climate factors directly influence yield, this study describes the development of a sensor network for climate monitoring of management zones (microclimates), allowing the identification of climate factors that influence yield at each of its stages.•Application of the internet of things to assist in decision making in the agricultural production system.•AgDataBox (ADB-IoT) web platform has an Application Programming Interface (API).•An agrometeorological station capable of monitoring all meteorological parameters was developed (Kate 3.0).

Growing degree-hours and degree-days in two management zones for each phenological stage of wheat (Triticum aestivum L.).

Monitoring the climatic conditions of crops is essential for smart agriculture development and adaptation of agricultural systems in the era of global change. Thereby, it is possibly better to understand the stages of development of the crop, thus adopting management practices more efficiently and planning the harvest with greater accuracy. This study was developed to analyze the growing degree-hours and degree-days in two management zones (MZs) for each phenological stage of wheat (Triticum aestivum L.) and the application of low-cost agroclimatological stations to monitor the climatic conditions of the field production. The study was developed in a Ferralsol in Céu-Azul/Brazil. Ten low-cost agrometeorological stations were installed in two MZs delineated based on elevation data using the web platform AgDataBox. Data on solar radiation, atmospheric pressure, wind speed, precipitation, relative humidity, air, and soil temperature were evaluated over two wheat crop seasons. Our results showed different climatic conditions, especially humidity and temperature, between MZs and crop seasons, which could probably cause yield variability. By the low-cost agroclimatological stations, it is possible to collect data on the thermal accumulation by the culture in growing degree-hours, which is a more accurate parameter than the growing degree-days (commonly used in similar studies). With the growing degree-hours data, it was possible to follow the development of the phenological stages of wheat. In conclusion, the results obtained suggest the importance of evaluating agroclimatological parameters in monitoring wheat crops. However, more studies are needed in regions with greater slopes, which may have microclimates that intensely influence the crop.

High Blood Pressure Is Associated with Tubulointerstitial Damage along with Glomerular Damage in Glomerulonephritis. A large Cohort Study.

The key role of arterial hypertension in chonic kidney disease (CKD) progression is widely recognized, but its contribution to tubulointerstitial damage (TID) in glomerulonephritis (GN) remains uncertain. Hence, the objective of this study is to clarify whether TID is associated with glomerular damage, and whether the damage at the tubulointerstitial compartment is more severe in hypertensive patients. The study included retrospectively consecutive patients referred to the Nephrology Unit with diagnoses of primary glomerulonephritis, lupus nephritis (LN), and nephroangiosclerosis (NAS) at biopsy. At least six glomeruli per biopsy were analysed through light and immunofluorescence microscopy. Global glomerulosclerosis (GGS%), TID, and arteriolar hyalinosis (AH) were used as markers of CKD severity. Of the 448 patients of the cohort, 403 received a diagnosis of GN, with the remaining being diagnosed with NAS. Hypertension was found in 52% of the overall patients, with no significant differences among those with GN, and reaching 88.9% prevalence rate in NAS. The hypertensive patients with GN had more marked damage in glomerular and tubular compartments than normotensives independently of the amount of proteinuria. Moreover, hypertension and GGS% were found to be strongly associated with TID in GN. In GN patients, not only the severity of glomerular damage but also the extent of TID was associated with high blood pressure.

Urinary N-acetyl-ß-glucosaminidase and estimated Glomerular filtration rate may identify patients to be treated with immuno-suppression at diagnosis in idiopathic membranous nephropathy.

AIM: The clinical course of idiopathic membranous nephropathy (IMN) varies from spontaneous remission of nephrotic syndrome (NS) to end-stage renal disease (ESRD). The aim of the study was baseline identification of patients with high risk of progression for which immunosuppressive therapy is mandatory. METHODS: Eighty-six IMN subjects were followed for a median of 69 months (range 6-253). Receiver operating characteristic curve and Cox proportional hazards model were used to evaluate prognostic factors for progression, defined as ESRD or estimated glomerular filtration rate (eGFR) reduction ≥50% of baseline. RESULTS: Among all, 24 subjects had progression. Area under the ROC curve of N-acetyl-ß-glucosaminidase/creatinine ratio (NAG/C) were significantly higher than proteinuria/24 h (0.770 and 0.637 respectively, P = 0.018). In Cox proportional hazards regression analysis, NAG/C and eGFR were independent predictors of progression. Compared to lowest tertile of NAG/C (<9.4 UI/gC) or highest tertile of eGFR (≥88 mL/min per 1.73m2 ), the multivariable-adjusted hazard ratio of highest tertile of NAG/C (≥19.2) was 18.97 (95%CI, 1.70-211.86) and lowest tertile of eGFR (<59) was 11.58 (95%CI, 2.02-66.29). Subjects with high NAG/C or low eGFR (high-risk, n = 43) had greater progression rate compared to moderate to low NAG/C and high eGFR (low-risk, n = 43) with or without NS at baseline (Log-rank test P = 0.001 and 0.006, respectively). In NS subjects (n = 65), high-risk group progression rate was significantly higher (91% vs. 29%, P = 0.003) and remission rate significantly lower (0% vs. 42%, p < 0.001) in non-immunosuppressed compared to steroids and cyclophosphamide treated patients; no significant differences were observed in low-risk group. CONCLUSION: Idiopathic membranous nephropathy subjects with high NAG/C and low eGFR have greater risk of progression, and immunosuppressive treatment is suggested at diagnosis.

Productivity of soybean in management zones with application of different sowing densities / Produtividade da soja em zonas de manejo com a aplicação de diferentes densidades de semeadura

ABSTRACT: The present study aimed to assess the efficiency of sowing at variable rates for soybean cultivation in two management zones (MZs) which were defined based on stable attributes and correlated with productivity using the Fuzzy C-means clustering algorithm and the kriging interpolation.Seeding was carried out in the 2015/2016 and 2017/2018 crops with a variation of 20% of seeds and crop row spacing of 0.70m. In each MZ, 8 plots with higher and lower seed density were established. Productivity was measured using a harvest monitor connected to a harvester. Data were filtered and submitted to descriptive analysis. Productivity maps were generated using the inverse square distance interpolation for each seeding density. In the MZ with the highest productive potential (MZ 1), the productivity was 3.39 and 3.18t ha-1, and in the MZ with the lowest productive potential (MZ 2) the productivity was 3.30 and 3.11t ha-1 for the years 2016 and 2018, respectively. Interpolation estimated higher productivity with the application of 15 plants m-1. Based on the economic analysis, it is suggested in this study the application of 214,000 plants ha-1 in both MZs.

RESUMO: O trabalho avaliou a eficiência da semeadura à taxa variada para cultura da soja em duas zonas de manejo (ZMs), as quais foram definidas com base em atributos estáveis e correlacionados com a produtividade, por meio do algoritmo de agrupamento Fuzzy C-means e o interpolador krigagem. A semeadura foi realizada nas safras 2015/2016 e 2017/2018, com variação de 20% de sementes e espaçamento entre linhas de 0,70m. Em cada ZM foram estabelecidas 8 parcelas em que variou-se maior e menor densidade de sementes. A produtividade foi medida com monitor de colheita acoplado em uma colhedora. Os dados foram filtrados e submetidos à análise descritiva, os mapas de produtividade foram gerados utilizando-se o interpolador inverso do quadrado da distância para cada densidade de semeadura. Na ZM com maior potencial produtivo (ZM 1) a produtividade foi de 3,39 e 3,18t ha-1, na ZM de menor potencial produtivo (ZM 2) foi de 3,30 e 3,11t ha-1, para os anos de 2016 e 2018, respectivamente. O interpolador estimou maior produtividade com a aplicação de 15 plantas m-1; pela análise econômica, sugere-se, dentro do estudado, a aplicação de 214.000 plantas ha-1 nas duas ZMs.

High (≥6.5) Spontaneous and Persistent Urinary pH Is Protective of Renal Function at Baseline and during Disease Course in Idiopathic Membranous Nephropathy.

Metabolic acidosis correction in advanced renal failure slows renal function decline attributed to tubulointerstitial damage (TID) reduction. No study evaluated if spontaneous baseline high urinary pH (UpH) is renoprotective in patients with normal renal function and without metabolic acidosis. The study tested this hypothesis in idiopathic membranous nephropathy (IMN). Eighty-five patients (follow-up 81 ± 54 months) measured UpH, serum creatinine, eGFR, protein/creatinine ratio, fractional excretion of albumin, IgG, α1-microglobulin, and urinary N-acetyl-ß-D-glucosaminidase (ß-NAG)/creatinine ratio. Twenty-eight patients (33%) had UpH ≥ 6.5 and 57 (67%) pH < 6.5; high versus low UpH patients had significantly lower values of the tubulointerstitial damage (TID) markers FE α1m and ß-NAG and significantly better baseline renal function. These differences persisted over time in a subset of 38 patients with 5 measurements along 53 ± 26 months. In 29 patients with nephrotic syndrome (NS) treated with supportive therapy (follow-up: 80 ± 52 months) renal function was stable in 10 high and significantly worse in 19 low UpH patients. Steroids + cyclophosphamide treatment in 35 NS patients masks the renoprotection of high UpH. Conclusions. In IMN high and persistent UpH is associated with reduction of the proteinuric markers of tubulointerstitial damage and baseline better renal function in all patients and in NS patients treated only with supportive therapy during disease course. The factors associated with high pH-dependent renoprotection were lower values of TID markers, eGFR ≥ 60 mL/min, BP < 140/90 mmHg, and age < 55 years.

Tubular reabsorption of high, middle and low molecular weight proteins according to the tubulo-interstitial damage marker N-acetyl-ß-D-glucosaminidase in glomerulonephritis.

BACKGROUND: Proteinuria, the hallmark of glomerular diseases, is an independent predictor of end-stage renal disease (ESRD) progression. Proteinuria is a mixture of proteins of different molecular weight (MW) dependent on alterations of glomerular filtration barrier (GFB) and reabsorption impairment by proximal tubular epithelial cells (PTECs). We aimed to evaluate the excretion of different-MW proteins according to the tubulo-interstitial damage marker N-acetyl-ß-D-glucosaminidase (NAG) in glomerulonephritides (GNs). METHODS: In 189 patients [idiopathic membranous nephropathy (IMN) n = 84, primary focal segmental glomerulosclerosis (FSGS) n = 48, crescentic IgA nephropathy (CIgAN) n = 37, minimal change disease (MCD) n = 20] several urinary proteins were measured at biopsy: α2-macroglobulin/creatinine ratio; fractional excretion of IgG, transferrin, albumin and α1-microglobulin, and the NAG/creatinine ratio divided by estimated glomerular filtration rate (eGFR) (NAG/C/eGFR), as NAG excretion is dependent on functioning nephron mass. Protein excretion was compared between 4th vs. 1st quartile of NAG/C/eGFR. RESULTS: In IMN, FSGS and CIgAN high-MW proteins excretion (α2-macroglobulin, IgG) was greater than that of middle- (transferrin, albumin) and low-MW proteins (α1-microglobulin) in 4th vs. 1st quartile of NAG/C/eGFR; the mean fold excretion increase of high-MW proteins in 3 GNs was 74.9, higher than that of middle- (34.8) and low-MW proteins (12.0). Higher excretion of high-MW proteins may be dependent on lower reabsorption by PTECs. By contrast, in MCD the difference in excretion of different-MW proteins is probably due to high GFB selectivity. CONCLUSION: High-MW protein excretion is dependent on GFB alteration and reduced reabsorption; its prognostic significance is ominous because in several glomerular diseases progression is associated with high-MW protein excretion.

Arteriolar hyalinosis and arterial hypertension as possible surrogate markers of reduced interstitial blood flow and hypoxia in glomerulonephritis.

BACKGROUND: In glomerulonephritis the final common pathway to end-stage renal disease (ESRD) is tubulo-interstitial damage (TID) whose main determinants are proteinuria and hypoxia consequent to haemodynamic and vascular alterations that reduce interstitial blood flow. Since oxygen tension is difficult to measure in human disease, arteriolar hyalinosis and arterial hypertension have been considered as possible surrogate markers of interstitial hypoxia. METHODS: The relationship between TID and arteriolar hyalinosis and arterial hypertension was evaluated in 132 IgA nephropathy (IgAN) and 79 idiopathic membranous nephropathy (IMN) patients. At biopsy tubulo-interstitial damage and arteriolar hyalinosis score were semi-quantitatively evaluated; urinary protein/creatinine ratio (P/C), fractional excretion (FE) of α1-microglobulin, urinary ß-NAG/creatinine ratio (NAG/C/eGFR) and urinary SDS-PAGE pattern were measured. RESULTS: In IgAN arteriolar hyalinosis (AH) score correlates with TID score (P < 0.0001), FE α1m (P = 0.004) and NAG/C/eGFR (P = 0.001), but not with P/C (P = 0.10). Patients with or without AH were different in terms of global glomerulosclerosis (GGS: P < 0.001), TID score (P < 0.001), FE α1m (P = 0.015), NAG/C/eGFR (P = 0.002), but not of P/C (P = 0.19). In IMN AH score correlates with TID score (P < 0.0001), FEα1m (P = 0.04), NAG/C/eGFR (P = 0.001), SDS-PAGE pattern (P = 0.018), but not with P/C (P = 0.10). Patients with or without AH were different in term of GGS% (P = 0.05), TID score (P = 0.001), FE α1m (P = 0.039), NAG/C/eGFR (P = 0.001), SDS-PAGE pattern (P = 0.02), but not of P/C (P = 0.065). Similar results for normal versus high blood pressure. CONCLUSIONS: Arteriolar hyalinosis and arterial hypertension, associated with TID and GGS, factors that reduce interstitial capillary bed and blood flow, may be considered as reliable surrogate markers of hypoxia and co-determinants of TID.

Fractional excretion of IgG in idiopathic membranous nephropathy with nephrotic syndrome: a predictive marker of risk and drug responsiveness.

BACKGROUND: Treatment of idiopathic membranous nephropathy with nephrotic syndrome is still controversial. There is currently little known about the clinical use of renal biomarkers which may explain contradictory results obtained from clinical trials. In order to assess whether IgG-uria can predict the outcome in membranous nephropathy, we examined the value of baseline EF-IgG in predicting remission and progression of nephrotic syndrome. METHODS: In a prospective cohort of 84 (34 female) idiopathic membranous nephropathy patients with nephrotic syndrome we validated the ability of the clinically available urine biomarker, IgG, to predict the risk of kidney disease progression and the beneficial effect of immunosuppression with steroids and cyclophosphamide. The fractional excretion of IgG (FE-IgG) and α1-microglobulin (FE-α1m), urine albumin/creatinine ratio, and eGFR were measured at the time of kidney biopsy. Primary outcome was progression to end stage kidney failure or kidney function (eGFR) decline ≥ 50% of baseline. Patients were followed up for 7.2 ± 4.1 years (range 1-16.8). RESULTS: High FE-IgG (≥ 0.02) predicted an increased risk of kidney failure (Hazard Ratio, (HR) 8.2, 95%CI 1.0-66.3, p=0.048) and lower chance of remission (HR 0.18, 95%CI 0.09-0.38, p<0.001). The ten-year cumulative risk of kidney failure was 51.7% for patients with high FE-IgG compared to only 6.2% for patients with low FE-IgG. During the study, only 24% of patients with high FE-IgG entered remission compared to 90% of patients with low FE-IgG. Combined treatment with steroids and cyclophosphamide decreased the progression rate (-40%) and increased the remission rate (+36%) only in patients with high FE-IgG. CONCLUSION: In idiopathic membranous nephropathy patients with nephrotic syndrome, FE-IgG could be useful for predicting kidney disease progression, remission, and response to treatment.

Urinary IgG and α2-macroglobulin are powerful predictors of outcome and responsiveness to steroids and cyclophosphamide in idiopathic focal segmental glomerulosclerosis with nephrotic syndrome.

OBJECTIVE: To assess whether high-molecular-weight proteins excretion predicts outcome and therapy-responsiveness in patients with FSGS and nephrotic syndrome. RESEARCH DESIGN AND METHODS: Thirty-eight patients measured at biopsy fractional excretion of IgG (FEIgG) and urinary α2-macroglobulin/creatinine ratio ( α m/C). Low and high risk groups were defined by cutoffs assessed by ROC analysis. In all patients first-line therapy was with steroids alone or in combination with cyclophosphamide. RESULTS: α2m/C and FEIgG were correlated with segmental sclerosis (r = 0.546; r = 0.522). Twenty-three patients (61%) entered Remission and 9 (24%) progressed to ESRD. Comparing low and high risk groups, by univariate analysis remission was predicted by FEIgG (77% versus 25%, P = 0.016) and α2m/C (81% versus 17%, P = 0.007) and ESRD at best by FEIgG (0% versus 75%, P < 0.0001) and α2m/C (4% versus 67%, P < 0.0001). By multivariate analysis FEIgG was the only independent predictor of remission and α2m/C the most powerful predictor of ESRD. Low and high risk groups of FEIgG and α2m/C in combination had very high predictive value of sustained remission and ESRD in response to therapy. CONCLUSIONS: FEIgG and α2m/C are powerful predictors of outcome and responsiveness to steroids and cyclophosphamide; their predictive value, if validated in prospective studies, may be useful in clinical practice suggesting first-line alternative treatments in high risk patients.

Validation of some pathophysiological mechanisms of the CKD progression theory and outcome prediction in IgA nephropathy.

BACKGROUND: The "remnant kidney" chronic kidney disease (CKD) progression theory based on hemodynamic, proteinuric and inflammatory mechanisms consequent to nephron loss has not been confirmed in a human disease. The aim of this study was to evaluate whether some of these mechanisms are present in IgA nephropathy (IgAN) and predict functional outcome. METHODS: In 132 IgAN patients (68 untreated, 64 angiotensin-converting enzyme inhibitor [ACEi]-treated) fractional excretion of IgG (FEIgG) and α1-microglobulin, proteinuria/day and ß-NAG excretion were divided by percentage of nonglobally sclerotic glomeruli ("surviving glomeruli" [SG]) to assess the effective glomerular loss and tubular load of proteins in surviving nephrons. Proteinuric markers were compared between 4 SG groups: group 1: ≤50%; group 2: >50% and <80%; group 3: ≥80% and <100%; and group 4: 100%. The outcome prediction (estimated glomerular filtration rate [eGFR] improvement and stability, progression) was assessed comparing low- and high-risk groups for each marker. RESULTS: Proteinuric markers showed increasing values in parallel with reduction of percentages of SG (p<0.0001). FEIgG/SG, 40-fold higher in patients with SG ≤50% vs. SG=100% (0.00040 ± 0.00039 vs. 0.00001 ± 0.00002, p<0.0001), was the most powerful outcome predictor: in ACEi-untreated patients, FEIgG/SG less or greater than 0.00010 predicted eGFR improvement and stability (88% vs. 12%, p<0.0001) and end-stage renal disease (ESRD) + eGFR reduction ≥50% (2% vs. 87.5%, p<0.0001); ACEi treatment reduced ESRD+eGFR reduction ≥50%: 36% vs. 87.5% (p=0.002). In patients with FEIgG/SG <0.00010 the eGFR increase is significantly higher in ACEi-treated for ≥70 months versus ACEi-untreated with follow up ≥70 months (+35% ± 23% vs. +13% ± 8%, p=0.004). CONCLUSIONS: In IgAN, progressive nephron loss is associated with an increase of proteinuric markers of glomerular and tubular damage. FEIgG/SG is the best outcome predictor. These data represent the first validation in a human disease of some pathophysiological mechanisms of CKD progression theory.

Fractional urinary excretion of IgG is the most powerful predictor of renoprotection by ACE inhibitors in IgA nephropathy.

BACKGROUND: Several aspects of renoprotection by angiotensin-converting enzyme inhibitors (ACEi) in IgA nephropathy (IgAN) are poorly defined: factors affecting responsiveness, role of proteinuria components and histological lesions, and criteria to identify patients who may benefit from ACEi. METHODS: In an observational study of 140 IgAN patients (follow up 62 +/- 36 months), 73 untreated and 67 ACEitreated for 53 +/- 28 months, 9 baseline risk factors (RFs) (blood pressure, serum creatinine, proteinuria/day, fractional excretion of IgG [FEIgG] and alpha1-microglobulin, global and segmental [SS] glomerular sclerosis, tubulointerstitial damage and arteriolar hyalinosis [AH] score), each divided into 2 subgroups according to a cutoff with the highest sensitivity and specificity for progression, were evaluated for ability to predict renoprotection. Primary end point: end-stage renal disease (ESRD) and doubling of serum creatinine (sCr); secondary end point: increase >or=25% of sCr with last sCr >or=1.58 mg/dL; total progression: sum of end points. RESULTS: Patients with RFs below cutoffs did not benefit from ACEi. All clinical and proteinuric and 2 histological RFs (SS, AH score) with values above cutoffs showed significant reduction of progression in ACEitreated vs. untreated patients; FEIgG showed the highest prediction of renoprotection: ESRD/sCrx2: 20% vs. 62% (p=0.0004); total progression: 40% vs. 85% (p=0.0003). By multivariate analysis, independent predictors of progression were FEIgG, sCr and no ACEi treatment. Proteinuria reduction from -100% to -30%, spontaneous or after ACEi treatment, did not affect progression in treated vs. untreated patients (19% vs. 13%, p=0.85). Patients with proteinuria increased or reduced <30% showed a reduction of total progression if ACEi-treated (15% vs. 77%, p=0.0002). Presence of 1 clinical or proteinuric RF above the cutoff may be a criterion to identify patients who may benefit from ACEi. CONCLUSIONS: Renoprotection by ACEi is a multifactorial phenomenon: the best predictor of renoprotection is FEIgG, a marker of disruption of glomerular barrier to proteins; renoprotection depends not only on ability to reduce proteinuria, but probably also on antiinflammatory and antifibrotic activity.

In crescentic IgA nephropathy, fractional excretion of IgG in combination with nephron loss is the best predictor of progression and responsiveness to immunosuppression.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the relationship between proteinuric markers (urinary excretion of IgG, alpha2-macroglobulin, alpha1-microglobulin) and serum creatinine (sCr), histologic lesions, progression, and immunosuppression responsiveness in crescentic IgA nephropathy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Fractional excretion of IgG (FEIgG) and of alpha1-microglobulin and urinary excretion of alpha2-macroglobulin were evaluated in 37 patients, 23 treated with steroids and cyclophosphamide. For assessment of the effective tubular load of proteins in surviving nephrons, new markers that take into account not only the absolute excretion value but also nephron loss were obtained dividing proteinuric markers for percentage of nonobsolescent glomeruli (surviving glomeruli [SG]). For each parameter, low- and high-risk groups were defined according to cutoffs with the highest sensitivity and specificity for progression (ESRD/doubling sCr) assessed by receiver operating characteristic analysis; follow up was 60 +/- 40 mo. RESULTS: FEIgG/SG is the most powerful progression predictor: 5 versus 83% in all patients; in treated patients, 0 versus 89%, increased to 0 versus 100% by sCr and FEIgG/SG in combination (low risk: both markers or only one below cutoff (n = 15); high risk: both markers above cutoff (n = 8). The nonprogressors showed at last observation 65% proteinuria reduction and 10% sCr reduction. CONCLUSIONS: In crescentic IgA nephropathy, FEIgG/SG, which evaluates altered size selectivity in relation to nephron loss, is the best progression predictor. In treated patients, progression prediction was increased by FEIgG/SG and sCr in combination. Treatment may be restricted to low-risk patients.

Stenting of renal artery stenosis: is it beneficial in chronic renal failure?

BACKGROUND: The utility of renal artery stenting (RS) in preserving renal function (RF) is not well established. Our prospective study aimed to examine the clinical effects of RS in patients with proximal renal artery stenosis and chronic renal failure (CRF). METHODS: Fifty-two patients, with atherosclerotic renal artery stenosis (ARAS) and renal impairment underwent successful monolateral (33 patients) or global RS (19 patients: six bilateral stenting, two surgical solitary kidney and 11 functional solitary kidney). Patients were considered eligible if they had at least a mild renal impairment (serum creatinine (Cr) >1.5 mg/dL). To assess a significant change in RF, we compared the slopes of the regression lines derived from the reciprocal of Cr vs. time, plotted before and after stenting. Patients had a median post-procedure follow-up of 24 months (range 9-54). RESULTS: Before stenting all patients exhibited a negative slope, indicating progressive renal failure. After stenting the slopes became positive in eight patients (15.5%), indicating a significant improvement in RF; in 31 patients (59.5%) the slopes were not significantly different from 0 and were associated with a stable RF, while 13 patients (25%) presented negative slopes and showed a continuous reduction in RF. Previous serum Cr, initial diameter of the treated kidney, vascular resistive index, and mono vs. global stenting were not significantly associated to post stenting RF. CONCLUSIONS: RS appears to be associated with RF stabilization in the majority of patients with CRF.

Urinary protein and enzyme excretion as markers of tubular damage.

PURPOSE OF REVIEW: In this review we intend to evaluate the clinical usefulness of measurement of urinary excretion of microproteins and tubular enzymes. RECENT FINDINGS: Studies of patients with acute tubular necrosis showed that the excretion of some well known enzymes and of new markers such as kidney injury molecule-1 has higher value than classic renal function tests for the early detection of the disease as well as for the prediction of the development of overt acute renal failure. Tubular dysfunction may be detected by measurement of the excretion of tubular enzymes and microproteins not only in workers chronically exposed to heavy metals but also in population exposed to low environmental level below the limits set by the WHO. In chronic glomerulonephritis the excretion of alpha1-microglobulin is significantly associated with the extent of tubulo-interstitial damage and predicts outcome better than proteinuria/day; in the same diseases NAG excretion is significantly dependent on immunoglobulin G and alpha1-microglobulin excretion and predicts remission, progression and response to therapy. SUMMARY: The measurement of urinary excretion of tubular enzymes and microproteins may be clinically useful in several different kidney diseases (such as acute tubular necrosis, glomerulonephritis) both for diagnosis and prediction of fractional outcome.

Pathophysiology of proteinuria.

Proteinuria is consequence of two mechanisms: the abnormal transglomerular passage of proteins due to increased permeability of glomerular capillary wall and their subsequent impaired reabsorption by the epithelial cells of the proximal tubuli. In the various glomerular diseases, the severity of disruption of the structural integrity of the glomerular capillary wall correlates with the area of the glomerular barrier being permeated by "large" pores, permitting the passage in the tubular lumen of high-molecular-weight (HMW) proteins, to which the barrier is normally impermeable. The increased load of such proteins in the tubular lumen leads to the saturation of the reabsorptive mechanism by the tubular cells, and, in the most severe or chronic conditions, to their toxic damage, that favors the increased urinary excretion of all proteins, including low-molecular-weight (LMW) proteins, which are completely reabsorbed in physiologic conditions. Recent clinical studies showed that in patients with glomerular diseases the urinary excretion of some HMW proteins [immunoglobulins G and M (IgG and IgM)] and of some LMW proteins, alpha1-microglobulin, beta2-microglobulin, correlates with the severity of the histologic lesions, and may predict, better than the quantity of proteinuria, the natural course, the outcome, and the response to treatment. It is suggested that some patients have already, at the time of clinical presentation, a structural damage of the glomerular capillary wall (injury of podocytes) and of the tubulointerstitium, the severity and scarce reversibility of which are reliably indicated by an elevated urinary excretion of HMW and LMW proteins.

Fractional excretion of IgG predicts renal outcome and response to therapy in primary focal segmental glomerulosclerosis: a pilot study.

BACKGROUND: Prolonged treatment with steroids and/or cyclophosphamide improves the prognosis of primary focal segmental glomerulosclerosis (FSGS). In nephrotic patients, no clinical or histological feature predicts responsiveness to therapy. METHODS: In 50 patients with FSGS, fractional excretion (FE) of immunoglobulin G (IgG), albumin, transferrin, and alpha(1)-microglobulin (alpha(1)m) was calculated. The aim of the study is to assess whether FE IgG and FE alpha(1)m: (1) correlate with histological lesions, (2) predict outcome, and (3) may be useful to guide therapy. RESULTS: The association of FE IgG with percentage of glomeruli with segmental sclerosis was at the limit of significance (P = 0.01). FE alpha(1)m was associated with extent of tubulointerstitial damage (P = 0.008). By multiple regression analysis, FE alpha(1)m was dependent on FE IgG (R(2) = 0.76; P = 0.000). The predictive value of proteinuric variables on outcome was evaluated in 29 patients with nephrotic syndrome and baseline normal renal function (serum creatinine level, 1.04 +/- 0.22 mg/dL [92 +/- 19 micromol/L]; follow-up, 50 +/- 33 months); remission rates were 91% and 0% in patients with FE IgG less than versus greater than 0.140 (P = 0.0009). By multiple logistic regression analysis, only FE IgG was associated with remission (P = 0.043). Proteinuria less than versus greater than 7.5 g/d of protein predicted end-stage renal failure (0% versus 36%; P = 0.004); the predictive value of FE IgG less than versus greater than 0.140 was higher (0% versus 71%; P = 0.0000). Patients with FE IgG less than 0.025 were responsive to steroids alone (70%) or steroids and cyclophosphamide (20%); patients with FE IgG greater than 0.025 and less than 0.140 were responsive to steroids alone (20%) or steroids and cyclophosphamide (80%); and 100% of patients with FE IgG greater than 0.140 were unresponsive to therapy (P = 0.000). CONCLUSION: In FSGS, FE IgG is at the limit of statistically significant association with segmental sclerosis, and FE alpha(1)m is associated with extent of tubulointerstitial damage. FE IgG shows the best predictive value for remission, progression, and response to therapy and may be useful to guide treatment. Am J Kidney Dis 41:328-335.