Transplantation of committed pre-adipocytes from brown adipose tissue improves whole-body glucose homeostasis.

Obesity and its co-morbidities including type 2 diabetes are increasing at epidemic rates in the U.S. and worldwide. Brown adipose tissue (BAT) is a potential therapeutic to combat obesity and type 2 diabetes. Increasing BAT mass by transplantation improves metabolic health in rodents, but its clinical translation remains a challenge. Here, we investigated if transplantation of 2-4 million differentiated brown pre-adipocytes from mouse BAT stromal fraction (SVF) or human pluripotent stem cells (hPSCs) could improve metabolic health. Transplantation of differentiated brown pre-adipocytes, termed "committed pre-adipocytes" from BAT SVF from mice or derived from hPSCs improves glucose homeostasis and insulin sensitivity in recipient mice under conditions of diet-induced obesity, and this improvement is mediated through the collaborative actions of the liver transcriptome, tissue AKT signaling, and FGF21. These data demonstrate that transplantation of a small number of brown adipocytes has significant long-term translational and therapeutic potential to improve glucose metabolism.

Autosomal dominant ApoA4 mutations present as tubulointerstitial kidney disease with medullary amyloidosis.

Sporadic cases of apolipoprotein A-IV medullary amyloidosis have been reported. Here we describe five families found to have autosomal dominant medullary amyloidosis due to two different pathogenic APOA4 variants. A large family with autosomal dominant chronic kidney disease (CKD) and bland urinary sediment underwent whole genome sequencing with identification of a chr11:116692578 G>C (hg19) variant encoding the missense mutation p.L66V of the ApoA4 protein. We identified two other distantly related families from our registry with the same variant and two other distantly related families with a chr11:116693454 C>T (hg19) variant encoding the missense mutation p.D33N. Both mutations are unique to affected families, evolutionarily conserved and predicted to expand the amyloidogenic hotspot in the ApoA4 structure. Clinically affected individuals suffered from CKD with a bland urinary sediment and a mean age for kidney failure of 64.5 years. Genotyping identified 48 genetically affected individuals; 44 individuals had an estimated glomerular filtration rate (eGFR) under 60 ml/min/1.73 m2, including all 25 individuals with kidney failure. Significantly, 11 of 14 genetically unaffected individuals had an eGFR over 60 ml/min/1.73 m2. Fifteen genetically affected individuals presented with higher plasma ApoA4 concentrations. Kidney pathologic specimens from four individuals revealed amyloid deposits limited to the medulla, with the mutated ApoA4 identified by mass-spectrometry as the predominant amyloid constituent in all three available biopsies. Thus, ApoA4 mutations can cause autosomal dominant medullary amyloidosis, with marked amyloid deposition limited to the kidney medulla and presenting with autosomal dominant CKD with a bland urinary sediment. Diagnosis relies on a careful family history, APOA4 sequencing and pathologic studies.

Quality of life among people living with HIV aged 50 years and over in Australia: Identifying opportunities to support better ageing.

OBJECTIVES: Improved life expectancy has led to an ageing population of people living with HIV in most countries. Research on ageing among people living with HIV has predominantly focused on physical and health-related quality of life rather than multidimensional quality of life. We measured quality of life among older people living with HIV in Australia and identified opportunities to guide the development and implementation of appropriate interventions. METHODS: In a national health and wellbeing survey of Australian people living with HIV, participants aged ≥50 years completed additional questions relevant to ageing. Quality of life was measured using PozQoL, a validated multidimensional instrument assessing quality of life among people living with HIV (range 1-5). Exploratory bivariate analyses aimed to identify sociodemographic characteristics associated with quality of life. Adjusted linear regressions aimed to assess changes in PozQoL score associated with recent experiences (last 12 months) of four exposures: food insecurity, HIV-related stigma, isolation from the HIV community, and difficulties accessing non-HIV health services. RESULTS: Among 319 older people living with HIV, the mean PozQol score was 3.30 (95% confidence interval [CI] 3.20-3.39). In bivariate analyses, PozQol scores were significantly higher among participants who were older (p = 0.006), had higher educational attainment (p = 0.009), were in a relationship (p = 0.005), were employed (p = 0.005), and had a higher income (p = 0.001). In adjusted regression models, PozQoL scores were lower among participants who reported recent experiences of food insecurity (ß -0.49; 95% CI -0.74 to -0.24), stigma (ß -0.53; 95% CI -0.73 to -0.33), isolation from the HIV community (ß -0.49; 95% CI -0.70 to -0.29), and difficulties accessing non-HIV health services (ß -0.50; 95% CI -0.71 to -0.30). CONCLUSIONS: Overall, older people living with HIV in this study had a moderate quality of life. Our findings suggest that HIV services should integrate programmes to support economic security and foster connections within the HIV community and across health services.

Clonal and Scalable Endothelial Progenitor Cell Lines from Human Pluripotent Stem Cells.

Human pluripotent stem cells (hPSCs) can be used as a renewable source of endothelial cells for treating cardiovascular disease and other ischemic conditions. Here, we present the derivation and characterization of a panel of distinct clonal embryonic endothelial progenitor cells (eEPCs) lines that were differentiated from human embryonic stem cells (hESCs). The hESC line, ESI-017, was first partially differentiated to produce candidate cultures from which eEPCs were cloned. Endothelial cell identity was assessed by transcriptomic analysis, cell surface marker expression, immunocytochemical marker analysis, and functional analysis of cells and exosomes using vascular network forming assays. The transcriptome of the eEPC lines was compared to various adult endothelial lines as well as various non-endothelial cells including both adult and embryonic origins. This resulted in a variety of distinct cell lines with functional properties of endothelial cells and strong transcriptomic similarity to adult endothelial primary cell lines. The eEPC lines, however, were distinguished from adult endothelium by their novel pattern of embryonic gene expression. We demonstrated eEPC line scalability of up to 80 population doublings (pd) and stable long-term expansion of over 50 pd with stable angiogenic properties at late passage. Taken together, these data support the finding that hESC-derived clonal eEPC lines are a potential source of scalable therapeutic cells and cell products for treating cardiovascular disease. These eEPC lines offer a highly promising resource for the development of further preclinical studies aimed at therapeutic interventions.

Fabry disease biomarkers in patients switched from enzyme-replacement therapy to migalastat oral chaperone therapy.

Background: A biomarker profile was evaluated longitudinally in patients with Fabry disease switched from enzyme-replacement therapy (ERT) to migalastat. Methods: 16 Gb3 isoforms and eight lyso-Gb3 analogues were analyzed in plasma and urine by LC-MS/MS at baseline and at three different time points in naive participants and participants switching from either agalsidase α or ß to migalastat. Results: 29 adult participants were recruited internationally (seven centers). The Mainz Severity Score Index and mean biomarker levels remained stable (p ≥ 0.05) over a minimum of 12 months compared with baseline following the treatment switch. Conclusion: In this cohort of patients with Fabry disease with amenable mutations, in the short term, a switch from ERT to migalastat did not have a marked effect on the average biomarker profile.

Variability of scan quality and perfusion density in longitudinal optical coherence tomography angiography imaging.

BACKGROUND/AIMS: Optical coherence tomography angiography (OCT-A) images are subject to variability, but the extent to which learning impacts OCT-A measurements is unknown. We determined whether there is a learning effect in glaucoma patients and healthy controls imaged with OCT-A. METHODS: Ninety-one open-angle glaucoma patients and 54 healthy controls were imaged every 4 months over a period of approximately 1 year in this longitudinal cohort study. We analysed 15°×15° scans, centred on the fovea, in one eye of each participant. Two-dimensional projection images for the superficial, intermediate and deep vascular plexuses were exported and binarised after which perfusion density was calculated. Linear mixed-effects models were used to investigate the association between perfusion density and follow-up time. RESULTS: The mean (SD) age of glaucoma patients and healthy controls was 67.3 (8.1) years and 62.1 (9.0) years, respectively. There was a significant correlation between perfusion density and scan quality in both glaucoma patients (r=0.50 (95% CI 0.42 to 0.58); p<0.05) and healthy controls (r=0.41 (95% CI 0.29 to 0.52); p<0.05). An increase in perfusion density occurred over time and persisted, even after adjustment for scan quality (1.75% per year (95% CI 1.14 to 2.37), p<0.01). CONCLUSIONS: Perfusion density measurements are subject to increasing experience of either the operator or participant, or a combination of both. These findings have implications for the interpretation of longitudinal measurements with OCT-A.

Safety and efficacy of pegunigalsidase alfa in patients with Fabry disease who were previously treated with agalsidase alfa: results from BRIDGE, a phase 3 open-label study.

BACKGROUND: Pegunigalsidase alfa is a novel, PEGylated α-galactosidase-A enzyme-replacement therapy approved in the EU and US to treat patients with Fabry disease (FD). OBJECTIVE/METHODS: BRIDGE is a phase 3 open-label, switch-over study designed to assess safety and efficacy of 12 months of pegunigalsidase alfa (1 mg/kg every 2 weeks) treatment in adults with FD who had been previously treated with agalsidase alfa (0.2 mg/kg every 2 weeks) for ≥ 2 years. RESULTS: Twenty-seven patients were screened; 22 met eligibility criteria; and 20 (13 men, 7 women) completed the study. Pegunigalsidase alfa was well-tolerated, with 97% of treatment-emergent adverse events (TEAEs) being of mild or moderate severity. The incidence of treatment-related TEAEs was low, with 2 (9%) discontinuations due to TEAEs. Five patients (23%) reported infusion-related reactions. Overall mean (SD; n = 22) baseline estimated glomerular filtration rate (eGFR) was 82.5 (23.4) mL/min/1.73 m2 and plasma lyso-Gb3 level was 38.3 (41.2) nmol/L (men: 49.7 [45.8] nmol/L; women: 13.8 [6.1] nmol/L). Before switching to pegunigalsidase alfa, mean (standard error [SE]) annualized eGFR slope was - 5.90 (1.34) mL/min/1.73 m2/year; 12 months post-switch, the mean eGFR slope was - 1.19 (1.77) mL/min/1.73 m2/year; and mean plasma lyso-Gb3 reduced by 31%. Seven (35%) out of 20 patients were positive for pegunigalsidase alfa antidrug antibodies (ADAs) at ≥ 1 study timepoint, two of whom had pre-existing ADAs at baseline. Mean (SE) changes in eGFR slope for ADA-positive and ADA-negative patients were + 5.47 (3.03) and + 4.29 (3.15) mL/min/1.73 m2/year, respectively, suggesting no negative impact of anti-pegunigalsidase alfa ADAs on eGFR slope. CONCLUSION: Pegunigalsidase alfa may offer a safe and effective treatment option for patients with FD, including those previously treated with agalsidase alfa. TRN: NCT03018730. Date of registration: January 2017.

The Impact of a Digital Weight Loss Intervention on Health Care Resource Utilization and Costs Compared Between Users and Nonusers With Overweight and Obesity: Retrospective Analysis Study.

BACKGROUND: The Noom Weight program is a smartphone-based weight management program that uses cognitive behavioral therapy techniques to motivate users to achieve weight loss through a comprehensive lifestyle intervention. OBJECTIVE: This retrospective database analysis aimed to evaluate the impact of Noom Weight use on health care resource utilization (HRU) and health care costs among individuals with overweight and obesity. METHODS: Electronic health record data, insurance claims data, and Noom Weight program data were used to conduct the analysis. The study included 43,047 Noom Weight users and 14,555 non-Noom Weight users aged between 18 and 80 years with a BMI of ≥25 kg/m² and residing in the United States. The index date was defined as the first day of a 3-month treatment window during which Noom Weight was used at least once per week on average. Inverse probability treatment weighting was used to balance sociodemographic covariates between the 2 cohorts. HRU and costs for inpatient visits, outpatient visits, telehealth visits, surgeries, and prescriptions were analyzed. RESULTS: Within 12 months after the index date, Noom Weight users had less inpatient costs (mean difference [MD] -US $20.10, 95% CI -US $30.08 to -US $10.12), less outpatient costs (MD -US $124.33, 95% CI -US $159.76 to -US $88.89), less overall prescription costs (MD -US $313.82, 95% CI -US $565.42 to -US $62.21), and less overall health care costs (MD -US $450.39, 95% CI -US $706.28 to -US $194.50) per user than non-Noom Weight users. In terms of HRU, Noom Weight users had fewer inpatient visits (MD -0.03, 95% CI -0.04 to -0.03), fewer outpatient visits (MD -0.78, 95% CI -0.93 to -0.62), fewer surgeries (MD -0.01, 95% CI -0.01 to 0.00), and fewer prescriptions (MD -1.39, 95% CI -1.76 to -1.03) per user than non-Noom Weight users. Among a subset of individuals with 24-month follow-up data, Noom Weight users incurred lower overall prescription costs (MD -US $1139.52, 95% CI -US $1972.21 to -US $306.83) and lower overall health care costs (MD -US $1219.06, 95% CI -US $2061.56 to -US $376.55) per user than non-Noom Weight users. The key differences were associated with reduced prescription use. CONCLUSIONS: Noom Weight use is associated with lower HRU and costs than non-Noom Weight use, with potential cost savings of up to US $1219.06 per user at 24 months after the index date. These findings suggest that Noom Weight could be a cost-effective weight management program for individuals with overweight and obesity. This study provides valuable evidence for health care providers and payers in evaluating the potential benefits of digital weight loss interventions such as Noom Weight.

Initial feasibility and challenges of hyperpolarized 129 Xe MRI in neonates with bronchopulmonary dysplasia.

PURPOSE: The underlying functional and microstructural lung disease in neonates who are born preterm (bronchopulmonary dysplasia, BPD) remains poorly characterized. Moreover, there is a lack of suitable techniques to reliably assess lung function in this population. Here, we report our preliminary experience with hyperpolarized 129 Xe MRI in neonates with BPD. METHODS: Neonatal intensive care patients with established BPD were recruited (N = 9) and imaged at a corrected gestational age of median:40.7 (range:37.1, 44.4) wk using a 1.5T neonatal scanner. 2D 129 Xe ventilation and diffusion-weighted images and dissolved phase spectroscopy were acquired, alongside 1 H 3D radial UTE. 129 Xe images were acquired during a series of short apneic breath-holds (˜3 s). 1 H UTE images were acquired during tidal breathing. Ventilation defects were manually identified and qualitatively compared to lung structures on UTE. ADCs were calculated on a voxel-wise basis. The signal ratio of the 129 Xe red blood cell (RBC) and tissue membrane (M) resonances from spectroscopy was determined. RESULTS: Spiral-based 129 Xe ventilation imaging showed good image quality and sufficient sensitivity to detect mild ventilation abnormalities in patients with BPD. 129 Xe ADC values were elevated above that expected given healthy data in older children and adults (median:0.046 [range:0.041, 0.064] cm2 s-1 ); the highest value obtained from an extremely pre-term patient. 129 Xe spectroscopy revealed a low RBC/M ratio (0.14 [0.06, 0.21]). CONCLUSION: We have demonstrated initial feasibility of 129 Xe lung MRI in neonates. With further data, the technique may help guide management of infant lung diseases in the neonatal period and beyond.

Pegloticase in Uncontrolled Gout: The Infusion Nurse Perspective.

Infused biologics, such as pegloticase, are a core component of managing uncontrolled gout, which is increasing in prevalence. Pegloticase is often the last line of therapy for patients with uncontrolled gout; therefore, achieving a successful course of treatment is critical. The infusion nurse's role in patient education, serum uric acid monitoring, and patient medication compliance is essential for ensuring patient safety and maximizing the number of patients who benefit from a full treatment course of pegloticase. Infusion nurses are on the front lines with patients and need to be educated on potential negative effects associated with the medications they infuse, such as infusion reactions, as well as risk management methods like patient screening and monitoring. Further, patient education provided by the infusion nurse plays a large role in empowering the patient to become their own advocate during pegloticase treatment. This educational overview includes a model patient case for pegloticase monotherapy, as well as one for pegloticase with immunomodulation and a step-by-step checklist for infusion nurses to refer to throughout the pegloticase infusion process. A video abstract is available for this article at http://links.lww.com/JIN/A105.

Can men 75 and older safely receive a minimally invasive radical prostatectomy?

Men 75 and older presenting with localized prostate cancer have traditionally not been managed with surgery. Therefore, we compared the morbidity and operative outcomes of radical prostatectomy (RP) in men 75 and older to their younger counterparts. We utilized the American College of Surgeons National Surgical Quality Improvement Program database to gather subjects who received a minimally invasive RP (CPT: 55866) from 2016 to 2020. This cohort was then stratified by age to compare men 18-74 years old and men 75 and older. The preclinical profile, complications, and outcomes were analyzed. Chi-square and Mann-Whitney U test were used to analyze categorical and continuous variables, respectively. Of the 48,485 men identified, 2,009 (4.1%) were ≥ 75 years old. Within the 75 and older cohort, the median age was 76 (IQR: 75-78), the median BMI was 27.3 (IQR: 24.9-29.9), and 1,601 (79.7%) were Caucasian. Men 75 and older had higher rates of Clavien 3 (1.3% vs. 0.8%, p = 0.02) and Clavien 4 (7.8% vs. 5.0%, p < 0.001) complications. Reoperative rates (1.7% vs. 1.1%, p = 0.01), readmission rates (6.5% vs. 4.1%, p < 0.001), and mortality (0.4% vs. 0.1%, p < 0.001) were all higher in men 75 and older. Multivariate analysis shows older age to be a risk factor for readmission (OR 1.58, 95%CI 1.31-1.90). Complications and 30-day outcomes remain within an acceptable range to offer surgery in men 75 and older. Age alone should not disqualify men from receiving a RP, but appropriate patient selection and counseling are necessary.

Persistent hematopoietic polyclonality after lentivirus-mediated gene therapy for Fabry disease.

The safety and efficacy of lentivirus-mediated gene therapy was recently demonstrated in five male patients with Fabry disease-a rare X-linked lysosomal storage disorder caused by GLA gene mutations that result in multiple end-organ complications. To evaluate the risks of clonal dominance and leukemogenesis, which have been reported in multiple gene therapy trials, we conducted a comprehensive DNA insertion site analysis of peripheral blood samples from the five patients in our gene therapy trial. We found that patients had a polyclonal integration site spectrum and did not find evidence of a dominant clone in any patient. Although we identified vector integrations near proto-oncogenes, these had low percentages of contributions to the overall pool of integrations and did not persist over time. Overall, we show that our trial of lentivirus-mediated gene therapy for Fabry disease did not lead to hematopoietic clonal dominance and likely did not elevate the risk of leukemogenic transformation.

Short-term structural and functional changes after airway clearance therapy in cystic fibrosis.

BACKGROUND: Airway clearance therapy (ACT) with a high-frequency chest wall oscillation (HFCWO) vest is a common but time-consuming treatment. Its benefit to quality of life for cystic fibrosis (CF) patients is well established but has been questioned recently as new highly-effective modulator therapies begin to change the treatment landscape. 129Xe ventilation MRI has been shown to be very sensitive to lung obstruction in mild CF disease, making it an ideal tool to identify and quantify subtle, regional changes. METHODS: 20 CF patients (ages 20.7 ± 5.1 years) refrained from performing ACT before arriving for a single-day visit. Multiple-breath washout (MBW), spirometry, Xe MRI, and ultrashort echo-time (UTE) MRI were obtained twice-before and after patients performed ACT using their prescribed HFCWO vests (average 4.7 ± 0.5 h). UTE MRIs were scored for structural abnormalities, and standard functional metrics were obtained from MBW, spirometry, and Xe MRI-FEV1,pp, LCI2.5, and VDPN4, respectively. RESULTS: Spirometry and Xe MRI detected significant improvements in lung function post-ACT. 15/20 patients showed improvements from a baseline median of 92% FEV1,pp. Similarly, 16/20 patients showed improvements in Xe MRI from a baseline median of 15.2% VDPN4. Average individual changes were +2.6% in FEV1,pp and -1.3% in VDPN4, but without spatial correlations to easily-identifiable causative structural defects (e.g. mucus plugs or bronchiectasis) on UTE MRI. CONCLUSIONS: Lung function improved after a single instance of HFCWO-vest ACT and was detectable by spirometry and Xe MRI. The only common structural abnormalities were mucus plugs, which corresponded to ventilation defects, but ventilation defects were often present without visible abnormalities.

Borderline personality features and altered social feedback processing in emerging adults: An EEG study.

The goal of this study was to examine social feedback processing among emerging adults with borderline personality features (BPF). Participants (N = 118; 66.9% female) completed ratings of BPF and a computerized peer interaction task designed to measure processing of rejection and acceptance cues at the neurophysiological (i.e., electroencephalogram [EEG]), behavioral, and self-report levels. When covarying symptoms of depression and social anxiety, greater BPF were associated with heightened neural processing of social acceptance cues, accounting for reactivity to neutral and rejection cues, as demonstrated by an enhanced reward positivity (RewP) component. Additionally, BPF were associated with less adaptive voting in response to peer acceptance, such that emerging adults with higher BPF made fewer votes to keep peers in the game who had provided acceptance feedback to participants. These neural and behavioral patterns associated with BPF highlight the potential role of social reward processing in borderline personality. Specifically, emerging adults high in BPF show a hyper-responsiveness to social acceptance at the neural level but difficulty modulating behavioral responses in an adaptive way to obtain more social rewards. Future research replicating these effects across development may guide efforts to address and prevent the profound social dysfunction associated with BPF.

The impact of supportive leadership on employee outcomes during organizational mergers: An organizational-level field study.

Past merger and acquisition research has reported mixed findings on the impact of mergers on workforces. To address these ambiguities and advance merger research at the organizational level of analysis, we present a natural quasi-experiment focusing on mergers in the English National Health Service. Building on organizational support theory and conservation of resources theory, we propose that merger events represent environmental stressors, with negative implications for employees' subjective (job satisfaction) and objective (absenteeism) outcomes. However, extending previous theorizing, we argue that by increasing their supportive leadership, midlevel management can compensate for the resource losses incurred during mergers, and in doing so, minimize the adverse impact on their workforces. We test our predictions in the context of multiple primary care trust mergers, which took place in 2006. We analyzed the annual staff surveys, combined with objective information on employee absenteeism, and compared merging organizations with nonmerging organizations before (2005) and after (2007) the mergers. As expected, employees of merging (vs. not merging) organizations showed stronger decreases in job satisfaction, and these decreases in subjective outcomes were associated with increases in absenteeism over the course of the merger process. However, consistent with our propositions, we found that increases in supportive leadership during the merger period served to mitigate these negative outcomes. Our results highlight the organizational-level implications of mergers and the role that midlevel management can play in compensating for the losses experienced during (stressful) merger events. We discuss the implications for dynamic models of merger integration and leadership during change. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Ni-Catalyzed Reductive Cross-Coupling of Cyclopropylamines and Other Strained Ring NHP Esters with (Hetero)Aryl Halides.

A nickel-catalyzed reductive cross-coupling of cyclopropylamine NHP esters with (hetero)aryl halides is reported. This efficient protocol provides direct access to 1-arylcyclopropylamines, a bioisosteric motif commonly used in small molecule drug discovery. The reaction proceeds rapidly (<2 h) with excellent functional group tolerance and without requiring heat- or air-sensitive reagents. The method can also be extended to the arylation of four-membered strained rings. The NHP esters are easily obtained from the corresponding commercially available carboxylic acids in one step with high yields and no column chromatography.

Safe, selective, and scalable carbenes.

The synthesis of reactive carbene intermediates is made simpler and safer.

Renoprotective Effect of Agalsidase Alfa: A Long-Term Follow-Up of Patients with Fabry Disease.

Fabry disease is a rare lysosomal storage disorder caused by mutations in the GLA gene, which, without treatment, can cause significant renal dysfunction. We evaluated the effects of enzyme replacement therapy with agalsidase alfa on renal decline in patients with Fabry disease using data from the Fabry Outcome Survey (FOS) registry. Male patients with Fabry disease aged >16 years at agalsidase alfa start were stratified by low (≤0.5 g/24 h) or high (>0.5 g/24 h) baseline proteinuria and by 'classic' or 'non-classic' phenotype. Overall, 193 male patients with low (n = 135) or high (n = 58) baseline proteinuria were evaluated. Compared with patients with low baseline proteinuria, those with high baseline proteinuria had a lower mean ± standard deviation baseline eGFR (89.1 ± 26.2 vs. 106.6 ± 21.8 mL/min/1.73 m2) and faster mean ± standard error eGFR decline (−3.62 ± 0.42 vs. −1.61 ± 0.28 mL/min/1.73 m2 per year; p < 0.0001). Patients with classic Fabry disease had similar rates of eGFR decline irrespective of baseline proteinuria; only one patient with non-classic Fabry disease had high baseline proteinuria, preventing meaningful comparisons between groups. In this analysis, baseline proteinuria significantly impacted the rate of eGFR decline in the overall population, suggesting that early treatment with good proteinuria control may be associated with renoprotective effects.