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Glomerular disease: looking beyond pathology.

ABSTRACT: The National Institute of Diabetes and Digestive and Kidney Diseases-supported Kidney Research National Dialogue asked the scientific community to formulate and prioritize research objectives aimed at improved understanding of kidney function and disease progression. Over the past 2 years, 1600 participants posted almost 300 ideas covering all areas of kidney disease. An overriding theme that evolved through these discussions is the need to move beyond pathology to take advantage of basic science and clinical research opportunities to improve diagnostic classification and therapeutic options for people with primary glomerular disease. High-priority research areas included focus on therapeutic targets in glomerular endothelium and podocytes, regenerating podocytes through developmental pathways, use of longitudinal phenotypically defined disease cohorts to improve classification schemes, identifying biomarkers, disease-specific therapeutics, autoantibody triggers, and changing the clinical research culture to promote participation in clinical trials. Together, these objectives provide a path forward for improving clinical outcomes of glomerular disease.

SUBMITTER: Wiggins RC

PROVIDER: S-EPMC4046719 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Glomerular disease: looking beyond pathology.

Wiggins Roger C RC Alpers Charles E CE Holzman Lawrence B LB He John C JC Salant David J DJ Chugh Sumant S SS Natarajan Rama R Trachtman Howard H Brasile Lauren L Star Robert A RA Rys-Sikora Krystyna E KE Moxey-Mims Marva M MM Flessner Michael F MF

Clinical journal of the American Society of Nephrology : CJASN 20140403 6

The National Institute of Diabetes and Digestive and Kidney Diseases-supported Kidney Research National Dialogue asked the scientific community to formulate and prioritize research objectives aimed at improved understanding of kidney function and disease progression. Over the past 2 years, 1600 participants posted almost 300 ideas covering all areas of kidney disease. An overriding theme that evolved through these discussions is the need to move beyond pathology to take advantage of basic scienc ...[more]

PMID: 24700796

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Project description:Key pointsPeak oxygen uptake, a primary determinant of prognosis, mortality and quality of life, is diminished in patients with chronic obstructive pulmonary disease (COPD), with mounting evidence supporting an important role for peripheral dysfunction, particularly within skeletal muscle. In patients with severe COPD and activity-matched controls, muscle oxygen transport and utilization were assessed at peak effort during single-leg knee-extensor exercise (KE), where ventilation is assumed to be submaximal. This strategy removes ventilation as the major constraint to exercise capacity in COPD, allowing maximal muscle function to be attained and evaluated. During maximal KE, both convective arterial oxygen delivery to the skeletal muscle microvasculature and subsequent diffusive oxygen delivery to the mitochondria were diminished in patients with COPD compared to control subjects. These findings emphasize the importance of factors, beyond the lungs, that influence exercise capacity in this patient population and may, ultimately, influence the prognosis, mortality and quality of life for patients with COPD.AbstractPeak oxygen uptake ( V?O2peak ), a primary determinant of prognosis, mortality and quality of life, is diminished in patients with chronic obstructive pulmonary disease (COPD). Mounting evidence supports an important role of the periphery, particularly skeletal muscle, in the diminished V?O2peak with COPD. However, the peripheral determinants of V?O2peak have not been comprehensively assessed in this cohort. Thus, the hypothesis was tested that both muscle convective and diffusive oxygen (O2 ) transport, and therefore skeletal muscle peak O2 uptake ( V?MO2peak ), are diminished in patients with COPD compared to matched healthy controls, even when ventilatory limitations (i.e. attainment of maximal ventilation) are minimized by using small muscle mass exercise. Muscle O2 transport and utilization were assessed at peak exercise from femoral arterial and venous blood samples and leg blood flow (by thermodilution) in eight patients with severe COPD (forced expiratory volume in 1s (FEV1 ) ± SEM = 0.9 ± 0.1 l, 30% of predicted) and eight controls during single-leg knee-extensor exercise. Both muscle convective O2 delivery (0.44 ± 0.06 vs. 0.69 ± 0.07 l min-1 , P < 0.05) and muscle diffusive O2 conductance (6.6 ± 0.8 vs. 10.4 ± 0.9 ml min-1 mmHg-1 , P < 0.05) were ?1/3 lower in patients with COPD than controls, resulting in an attenuated V?MO2peak in the patients (0.27 ± 0.04 vs. 0.42 ± 0.05 l min-1 , P < 0.05). When cardiopulmonary limitations to exercise are minimized, the convective and diffusive determinants of V?MO2peak , at the level of the skeletal muscle, are greatly attenuated in patients with COPD. These findings emphasize the importance of factors, beyond the lungs, that may ultimately influence this population's prognosis, mortality and quality of life.

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Glomerular disease: looking beyond pathology.

Publications

Glomerular disease: looking beyond pathology.

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