Abstract:
:Alport syndrome is experiencing a remarkable increase in preclinical investigations. To proactively address the needs of the Alport syndrome community, as well as offer clarity for future clinical research sponsors, the Alport Syndrome Foundation hosted a workshop to generate consensus recommendations for prospective trials for conventional drugs. Opinions of key stakeholders were carefully considered, including those of the biopharmaceutical industry representatives, academic researchers, clinicians, regulatory agency representatives, and-most critically-patients with Alport syndrome. Recommendations were established for preclinical researchers, the use and selection of biomarkers, standards of care, clinical trial designs, trial eligibility criteria and outcomes, pediatric trial considerations, and considerations for patient engagement, recruitment, and treatment. This paper outlines their recommendations.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Weinstock BA,Feldman DL,Fornoni A,Gross O,Kashtan CE,Lagas S,Lennon R,Miner JH,Rheault MN,Simon JF,Workshop Participants.doi
10.1016/j.kint.2020.02.029subject
Has Abstractpub_date
2020-06-01 00:00:00pages
1109-1116issue
6eissn
0085-2538issn
1523-1755pii
S0085-2538(20)30352-5journal_volume
97pub_type
杂志文章abstract::Whole-genome microarrays identify large numbers of gene expression changes that appear specifically related to disease states such as antineutrophil cytoplasmic autoantibody (ANCA) and systemic lupus erythematosus. Although understanding this enormous volume of esoteric data is difficult, a few basic concepts regardin...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5002492
更新日期:2007-10-01 00:00:00
abstract::Phagocyte-derived interleukin-12 (IL-12) is a key cytokine that induces the development of an effective Th1 type immune response in various inflammatory and infectious disorders. To determine the importance of IL-12 in the pathogenesis of autoimmune renal injury we examined the renal production of this heterodimeric c...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.10
更新日期:1997-01-01 00:00:00
abstract::To evaluate the underlying mechanism of the putative renal protective effects of angiotensin converting enzyme (ACE) inhibitors, the modulatory action of captopril on the angiotensin II (Ang II) and platelet-derived growth factor (PDGF)-induced increase of cytosolic free calcium concentration ([Ca2+]i) was investigate...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.323
更新日期:1994-09-01 00:00:00
abstract::IgA1 proteins from sera of patients with IgA nephropathy (IgAN) are galactosylated to a lesser degree than those from healthy controls. The increased reactivity of intact or de-sialylated serum IgA1 with N-acetylgalactosamine (GalNAc)-specific lectins, Helix aspersa (HAA) and Caragana arborescens (CAA) and de-sialylat...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.361
更新日期:1997-08-01 00:00:00
abstract::Inflammation is a protective response to remove dangerous stimuli from the body. The multiprotein complex called the inflammasome regulates inflammation through the cleavage of proinflammatory cytokines into mature forms. Shahzad et al. unravel the importance of the Nlrp3 inflammasome, especially activated in glomerul...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2014.322
更新日期:2015-01-01 00:00:00
abstract::Incorporation in vivo of labeled orotate into RNA and total nucleotides was measured in isolated glomeruli and whole renal cortex. In 2-day diabetic animals, glomerular RNA was increased, and there was greater incorporation of orotate into total nucleotides and RNA as compared with controls. Insulin reversed the exagg...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1981.166
更新日期:1981-10-01 00:00:00
abstract::Podocytes are highly differentiated cells that play an important role in maintaining glomerular filtration barrier integrity; a function regulated by small GTPase proteins of the Rho family. To investigate the role of Rho A in podocyte biology, we created transgenic mice expressing doxycycline-inducible constitutively...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.472
更新日期:2012-06-01 00:00:00
abstract::Hyperhomocysteinemia, an arteriosclerotic risk factor, persists in 75% of dialysis patients despite routine low dose supplementation with the B-vitamin co-factors/substrates for homocysteine (Hcy) metabolism, and normal or supernormal plasma status of these vitamins (Atherosclerosis 114:93, 1995). We conducted a place...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1038/ki.1996.19
更新日期:1996-01-01 00:00:00
abstract::Observational studies are valuable and provocative. We are learning about how we practice peritoneal dialysis (PD) and how we might improve on that practice. For example, outcomes of PD therapy are not worse in large patients. Perhaps this will encourage physicians and patients to utilize PD in large patients. In addi...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2009.65
更新日期:2009-07-01 00:00:00
abstract::The essential role of the glycoprotein hormone erythropoietin (Epo) in the control of red blood cell production is well established. Synthesis of Epo is induced in response to low oxygen (hypoxia). In response to stimulation, increases in serum Epo levels are paralleled by changes in the abundance of Epo mRNA. These c...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.70
更新日期:1997-02-01 00:00:00
abstract:BACKGROUND:The podocyte is the focus of much research into the mechanisms of renal disease progression, and the number of podocytes per glomerulus has thus become a parameter of much interest. When counting podocytes, the actual particle counted is the cell nucleus. The majority of published studies estimating podocyte...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1111/j.1523-1755.2004.00787.x
更新日期:2004-08-01 00:00:00
abstract::The kidneys excrete the daily acid load mainly by generating and excreting ammonia but the underlying molecular mechanisms are not fully understood. Here we evaluated the role of the inwardly rectifying potassium channel subunit Kir4.2 (Kcnj15 gene product) in this process. In mice, Kir4.2 was present exclusively at t...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2019.09.028
更新日期:2020-02-01 00:00:00
abstract:BACKGROUND:In addition to nitric oxide (NO) and prostacyclin (PGI2), the vascular endothelium can influence local vascular tone by a mechanism involving the hyperpolarization of vascular smooth muscle cells. This response is attributed to the release of an endothelium-derived hyperpolarizing factor (EDHF). The present ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00910.x
更新日期:2003-05-01 00:00:00
abstract::A morphometric technique is used to estimate the absolute and relative surface areas of the brush border microvilli and cell walls bordering lateral intercellular spaces. In isolated, perfused proximal tubule from rabbit, the luminal and lateral surfaces are equal in area. For proximal convoluted tubules (PCT) each su...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1975.125
更新日期:1975-12-01 00:00:00
abstract:BACKGROUND:Adrenomedullin (ADM) exerts antiproliferative effects on rat mesangial cells in vitro and, therefore is a possible renoprotective agent. In contrast, nitric oxide (NO) is capable of exerting both cytoprotective and cytotoxic actions. It was the objective of the present study to examine whether NO stimulates ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00330.x
更新日期:2002-05-01 00:00:00
abstract::The risk of death in hemodialysis patients treated with calcium-containing phosphate binders or sevelamer is not known. We assessed all-cause mortality in 127 patients new to hemodialysis assigned to calcium-containing binders or sevelamer after a median follow-up of 44 months from randomization. This was a predetermi...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/sj.ki.5002059
更新日期:2007-03-01 00:00:00
abstract:BACKGROUND:Renal failure and toxic acute tubular necrosis (ATN) may be seen following exposure to a variety of therapeutic agents. Zoledronate (Zometa) is a new, highly potent bisphosphonate used in the treatment of hypercalcemia of malignancy. We report the first clinical-pathologic study of nephrotoxicity associated ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00071.x
更新日期:2003-07-01 00:00:00
abstract::Medial arterial calcification involves chondrogenic/osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs). Zhao et al. report that phosphate activates the mammalian target of rapamycin (mTOR) cascade in VSMCs, leading to downregulation of Klotho. Furthermore, rapamycin was shown to halt medial calcif...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2015.223
更新日期:2015-10-01 00:00:00
abstract::The clinical utility of cisplatin is limited by nephrotoxicity. Oh et al. report that β-lapachone prevents this nephrotoxicity but not cisplatin's cytotoxicity for cancers. In addition to its potential clinical importance, the beneficial effect of β-lapachone on cisplatin acute kidney injury may illustrate fundamental...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2013.419
更新日期:2014-03-01 00:00:00
abstract::Residual renal function is a major survival determinant for peritoneal dialysis patients. Hypovolemia can cause acute kidney injury and loss of residual renal function, and it has been suggested that patients receiving peritoneal dialysis should preferably be maintained hypervolemic to preserve residual renal function...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.273
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Glucocorticoids (GC) represent the mainstay of treatment of idiopathic nephrotic syndrome (INS) and might be involved in the pathogenesis of the disease. We evaluated basal secretion of cortisol, number and affinity of glucocorticoid receptors, dexamethasone (Dex)-mediated inhibition of concanavalin-A (Con-A...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00392.x
更新日期:2004-02-01 00:00:00
abstract::The transition between the glomerulus and the proximal tubule was studied by light and electron microscopy in perfusion-fixed rabbit kidneys. In most nephrons a transitional segment of tubule occurred between the Bowman's capsule and the proximal tubule proper. This initial part of the tubule was lined by flattened ce...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1975.22
更新日期:1975-03-01 00:00:00
abstract::In this study, we have evaluated 50 children (30 girls and 20 boys; mean age, 10.1 years) with a variety of renal diseases in whom renal biopsy specimens showed crescents in greater than or equal to 50% of glomeruli. Initial clinical features included edema in 61%; hypertension in 51%; gross hematuria in 73%; 3 to 4+ ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1985.30
更新日期:1985-02-01 00:00:00
abstract::Tremendous progress has been made over recent years in the understanding of the mechanisms regulating calcium, phosphorus, vitamin D, and parathyroid hormone homeostasis in the normal human body and in patients with different degrees of renal failure. In addition, some of these findings have been translated into clini...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.692
更新日期:2009-05-01 00:00:00
abstract::To determine whether Cyclosporine A (CsA) alters the intrarenal expression of the renin and type 1 angiotensin II receptor genes, male adult Sprague-Dawley rats were given 25 mg/kg/day CsA s.c. for three weeks (CsA, N = 20) and were compared to pair-fed vehicle treated rats (Con, N = 20). The intrarenal distribution o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.90
更新日期:1993-03-01 00:00:00
abstract::Colony stimulating factor-1 (CSF-1) is a chemoattractant and growth factor for macrophages. In autoimmune MRL-lpr mice, CSF-1 is detected in the circulation and there is an increase in CSF-1 transcripts and macrophages in the kidney. The purpose of this study was to establish whether the MRL-lpr kidney is responsible ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.9
更新日期:1996-01-01 00:00:00
abstract::Although the goal glomerular filtration rate (GFR) for chronic dialysis initiation is currently above 5 ml/min per 1.73 m(2), there is no convincing evidence that patients will benefit from this approach. With close follow-up of advanced chronic kidney disease patients, aiming to start dialysis at an estimated GFR (eG...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2014.164
更新日期:2014-10-01 00:00:00
abstract::The circumstances under which furosemide increases renal blood flow was examined in mongrel dogs as it may relate to a tubuloglomerular feedback mechanism. Two maneuvers, desoxycorticosterone (DOCA) plus salt treatment and inhibition of tubular fluid flow, were used in the dogs to evaluate the renal vascular effects o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1980.158
更新日期:1980-10-01 00:00:00
abstract::Co-presentation with both ANCA and anti-GBM antibodies is thought to be relatively rare. Current studies of such 'double-positive' cases report small numbers and variable outcomes. To study this further we retrospectively analyzed clinical features and long-term outcomes of a large cohort of 568 contemporary patients ...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1016/j.kint.2017.03.014
更新日期:2017-09-01 00:00:00
abstract::In a double-blind, randomized, placebo-controlled cross-over study, we investigated in seven patients with chronic renal failure the effect of conjugated estrogens (0.6 mg/kg/day for 5 days) on template bleeding time and on thromboxane A2 (TxA2), beta-thromboglobulin (beta-TG) and prostacyclin (PGI2) concentrations in...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/ki.1990.331
更新日期:1990-12-01 00:00:00