Abstract:
:Patients with type 2 diabetes run a high risk for progressive renal function loss. Many interventions have been tested to reduce the risk, but we are nowadays still confronted with a high unmet need. To improve on this unmet need, we will have to change the current strategies in drug discovery, clinical trials and clinical practice. Target finding and the search for new interventions has to change to include more individual mechanistic approaches. Drugs will be selected on basis of finding the "individual" mechanism of renal function loss by looking at renal tissue biopsies or new biomarkers in urine or plasma. To test the promising drugs for clinical efficacy and safety and reduce the unmet need, trial design in type 2 diabetes will have to alter. First, selection of patients at risk for progression of renal function loss will need to be more specific. True progressors need to be identified by switching from classical risk determinants (low eGFR and high albuminuria) to new surrogates like steep eGFR slopes. In addition, the investigational drugs should only continue into registration trials in responder populations: patients that show a good response in the target/surrogate risk marker and no bad responses. This way we will improve the success of hard outcome trials, which has been poor in the past decade. We will reduce the unmet need and reduce the number of patients that are exposed to long term trial treatments without any benefit or even harm. Platform design and basket trials will catch the non-responders and switch them to other investigational drugs with different mechanism of action.Drug registration will be much more directed to the individual patients and will lead to improved individual patient medication advices and improved individual efficacy and safety. We are entering the era of precision medicine in nephrology.
journal_name
J Nephroljournal_title
Journal of nephrologyauthors
de Zeeuw Ddoi
10.1007/s40620-020-00820-2subject
Has Abstractpub_date
2020-12-01 00:00:00pages
1163-1169issue
6eissn
1121-8428issn
1724-6059pii
10.1007/s40620-020-00820-2journal_volume
33pub_type
杂志文章,评审abstract:BACKGROUND:The effect of interleukin-11 (IL-11) on transforming growth factor-ß (TGF-ß) is controversial and has not been examined in renal diseases. In this study, we (i) characterised the up-regulation of TGF-ß1, phospho-p38 MAPK (p-p38 MAPK) and extracellular matrix during pathogenesis of glomerulonephritis and (ii)...
journal_title:Journal of nephrology
pub_type: 杂志文章
doi:10.5301/jn.2010.5094
更新日期:2011-01-01 00:00:00
abstract::The term thin glomerular basement membrane disease (TBMD) refers to a condition characterised by thinning of the GBM at electron microscopy examination and, clinically, by isolated hematuria, frequently occurring in other family members, with no extra-renal manifestations. Progression towards chronic renal failure (CR...
journal_title:Journal of nephrology
pub_type: 杂志文章,评审
doi:
更新日期:2000-01-01 00:00:00
abstract:INTRODUCTION:Contrast-induced acute kidney injury, also referred to as contrast-induced nephropathy (CIN), is a potentially serious renal complication associated with the use of iodinated contrast media (CM) in patients at risk. With the dramatic growth in contrast-enhanced imaging services worldwide, including procedu...
journal_title:Journal of nephrology
pub_type: 杂志文章,评审
doi:
更新日期:2009-05-01 00:00:00
abstract:BACKGROUND:Chronic kidney disease is a risk factor for death in the year following myocardial infarction or coronary angioplasty. Whether the risk is similar after coronary stenting, whether impaired renal function is associated with an increased risk of cardiovascular death or myocardial infarction (MI) after coronary...
journal_title:Journal of nephrology
pub_type: 杂志文章,随机对照试验
doi:
更新日期:2006-11-01 00:00:00
abstract::The newly described endothelium-dependent vasoactive substances, nitric oxide and endothelins, have been the subject of intense investigative interest and have been demonstrated to promote a wide array of autocrine and paracrine functions. Recent data highlight their emerging role as potential important mediators of r...
journal_title:Journal of nephrology
pub_type: 杂志文章,评审
doi:
更新日期:1997-05-01 00:00:00
abstract::To maintain divalent ion concentration within the body, a complex sensor has evolved to identify the changes in the extracellular environment and cause the surrounding cells to either secrete or absorb in response to change. An important member of these "sensors" is the calcium-sensing receptor (CaSR), which is consta...
journal_title:Journal of nephrology
pub_type: 杂志文章,评审
doi:
更新日期:2010-11-01 00:00:00
abstract:AIM:The objective of this study was to determine whether the baseline estimated glomerular filtration rate (eGFR) level was independently associated with in-hospital mortality in generalized patients with hospital-acquired acute kidney injury (HA-AKI) in China. METHODS:All of the patients admitted to a tertiary medica...
journal_title:Journal of nephrology
pub_type: 杂志文章
doi:10.1007/s40620-015-0238-5
更新日期:2016-06-01 00:00:00
abstract::Hemolytic uremic syndrome (HUS) is a rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. It is usually secondary to infections by strains of Escherichia coli (STEC) that produce Shiga-like toxin. In about 10% of patients, no STEC infections are reported. In these ...
journal_title:Journal of nephrology
pub_type: 杂志文章,评审
doi:10.5301/jn.5000146
更新日期:2012-11-01 00:00:00
abstract:BACKGROUND:There is growing evidence of the potential properties of nitrate-rich foods against development of hypertension (HTN) and vascular disease. In this study, we investigated the association of nitrate-containing vegetables (NCVs) with risk of HTN after 3 years of follow-up. METHODS:This prospective study was c...
journal_title:Journal of nephrology
pub_type: 杂志文章
doi:10.1007/s40620-015-0229-6
更新日期:2016-06-01 00:00:00
abstract::That systemic hypertension is involved in the progression of human renal disease is mostly suggested by the way anti-hypertensive treatment affects the course of the disease. Clinical evidence has been obtained from observational studies as well as from studies of dietary protein restriction. In addition, several tria...
journal_title:Journal of nephrology
pub_type: 杂志文章,评审
doi:
更新日期:2000-05-01 00:00:00
abstract::It has been increasingly apparent that end-stage renal disease (ESRD) patients carry an inflammatory burden, which may play a pivotal role in the evolution of not only wasting but also of the massive increase in the relative risk of cardiovascular disease (CVD). Also increased oxidative stress (an impairment of the pr...
journal_title:Journal of nephrology
pub_type: 杂志文章,评审
doi:
更新日期:2004-11-01 00:00:00
abstract::Appropriate timing of starting chronic dialysis in patients with advanced chronic kidney disease (CKD) under nephrology care still is undefined. We systematically reviewed the most recent studies that have compared outcomes of stage 5-CKD under conservative versus substitutive treatment. Eleven studies, most in elderl...
journal_title:Journal of nephrology
pub_type: 杂志文章,评审
doi:10.1007/s40620-015-0243-8
更新日期:2016-04-01 00:00:00
abstract:INTRODUCTION:Lack of adherence may influence the efficiency of phosphate binders. Our clinical hypothesis was that if lanthanum carbonate (LC) might offer some advantage over sevelamer (S), that that would be in those patients in whom serum phosphate (P) levels were not controlled by S or in those requiring high doses ...
journal_title:Journal of nephrology
pub_type: 杂志文章
doi:
更新日期:2010-11-01 00:00:00
abstract::The aging process results in remarkable changes in the kidney. These changes are both anatomical and functional and have been considered the cause of the increased propensity of the elderly to acute or chronic renal failure. However, the majority of the early studies on aging enrolled institutionalized elderly patient...
journal_title:Journal of nephrology
pub_type: 杂志文章,评审
doi:
更新日期:2010-09-01 00:00:00
abstract:BACKGROUND:Incremental dialysis may preserve residual renal function and improve survival in comparison with full-dose dialysis; however, available evidence is limited. We therefore compared all-cause mortality and residual kidney function (RKF) loss in incremental and full-dose dialysis and time to full-dose dialysis ...
journal_title:Journal of nephrology
pub_type: 杂志文章,meta分析
doi:10.1007/s40620-018-00577-9
更新日期:2019-10-01 00:00:00
abstract::Late-presenting end-stage renal disease is a significant problem worldwide. Up to 70% of patients start dialysis in an unplanned manner without a definitive dialysis access in place. Haemodialysis via a central venous catheter is the default modality for the majority of such patients, and peritoneal dialysis is usuall...
journal_title:Journal of nephrology
pub_type: 杂志文章,评审
doi:10.1007/s40620-018-0485-3
更新日期:2019-02-01 00:00:00
abstract:BACKGROUND:With improvements in technology, renal biopsies have become safer and could potentially be effectively carried out in the outpatient setting. The purpose of our study is to compare the safety and cost of performing outpatient versus inpatient renal biopsies at a single Northern California pediatric hospital....
journal_title:Journal of nephrology
pub_type: 杂志文章
doi:
更新日期:2009-01-01 00:00:00
abstract::Calciphylaxis, or calcific uremic arteriolopathy, is a vascular ossification-calcification disease involving cutaneous or visceral arterioles, with ischemic damage of the surrounding tissues, usually in the setting of chronic kidney disease. Pathogenesis is still unclear and probably comprises the participation of vas...
journal_title:Journal of nephrology
pub_type: 杂志文章,评审
doi:10.1007/s40620-015-0192-2
更新日期:2015-10-01 00:00:00
abstract::Urine samples can be readily obtained from patients in everyday clinical practice. Therefore, the availability of urine allows physicians to obtain relevant clinical information in a timely manner. Since the measurement of urinary protein levels is essential in diagnosing and treating a host of diseases, the potential...
journal_title:Journal of nephrology
pub_type: 杂志文章,评审
doi:10.1007/s40620-020-00735-y
更新日期:2020-04-23 00:00:00
abstract:BACKGROUND:Previous studies have shown that bleeding times have positive predictive values of only 5% for perioperative bleeding in unselected populations. Nevertheless, performing bleeding times prior to all renal biopsies is common in nephrology practice. METHODS:We report complications of 112 renal biopsies done at...
journal_title:Journal of nephrology
pub_type: 杂志文章
doi:
更新日期:2001-07-01 00:00:00
abstract:BACKGROUND:Different mitogens are involved in the pathogenesis of kidney damage after subtotal nephrectomy. One of them, TGF-beta, controls mesangial cell proliferation and interstitial fibrosclerosis. The transduction of the TGF-beta signal is controlled by intracellular signalling molecules such as Ras G monomeric pr...
journal_title:Journal of nephrology
pub_type: 杂志文章
doi:
更新日期:2002-09-01 00:00:00
abstract:BACKGROUND:Because urinary low molecular weight protein (LMWP) measurement shows changes in renal integrity at an early stage, beta2-microglobulin (B2m), retinol-binding protein (RBP) and alpha1-microglobulin (A1m) were evaluated in 24-hour urine collection of 65 patients with pure monoclonal light chain (MLC) proteinu...
journal_title:Journal of nephrology
pub_type: 杂志文章
doi:
更新日期:2007-11-01 00:00:00
abstract:BACKGROUND:An increased number of major histocompatibility complex (MHC) class II-positive cells (OX-6+ cells) were observed in the glomerulus and periglomerular interstitium during the course of anti-glomerular basement membrane (anti-GBM) crescentic glomerulonephritis (GN) in WKY rats. This study aimed to demonstrate...
journal_title:Journal of nephrology
pub_type: 杂志文章
doi:
更新日期:2007-05-01 00:00:00
abstract::Preeclampsia (PE) is a protean syndrome causing a transitory kidney disease, characterised by hypertension and proteinuria, ultimately reversible after delivery. Its prevalence is variously estimated, from 3 to 5% to 10% if all the related disorders, including also pregnancy-induced hypertension (PIH) and HELLP syndro...
journal_title:Journal of nephrology
pub_type: 杂志文章,实务指引,评审
doi:10.1007/s40620-017-0390-1
更新日期:2017-06-01 00:00:00
abstract::Osteoporosis and chronic kidney disease (CKD) have both independently important potential impact on bone health. A significant number of patients with CKD stages 3a-5D have been shown to have low bone mineral density (BMD), leading to a strikingly elevated risk of fractures (mainly hip fractures) and higher associated...
journal_title:Journal of nephrology
pub_type: 杂志文章,评审
doi:10.1007/s40620-017-0404-z
更新日期:2017-10-01 00:00:00
abstract::Ambulatory blood pressure monitoring (ABPM) has been developed to overcome recognized deficiencies and inaccuracies of classic (office) BP measurements in the diagnosis and management of hypertension (HTN). Although in adults it has become a valuable tool for the diagnosis and ongoing management of HTN, and its use ha...
journal_title:Journal of nephrology
pub_type: 杂志文章,评审
doi:
更新日期:2004-09-01 00:00:00
abstract::Bisphosphonates inhibit bone resorption and are widely used to treat osteolytic metastases and osteoporosis. Renal osteodystrophy patients have continuous bone loss due to chronically elevated parathyroid hormone (PTH). In this open-label study, ibandronate was evaluated for the treatment of reduced bone density in re...
journal_title:Journal of nephrology
pub_type: 杂志文章,随机对照试验
doi:
更新日期:2008-07-01 00:00:00
abstract::Rapidly progressive glomerulonephritis (RPGN) is a rare occurrence in IgA nephropathy (IgAN) in renal transplant patients on immunosuppressive therapy. RPGN post ischemia-reperfusion has not been previously reported. We report a 62 year old male patient on azathioprine therapy, 9 years after left cadaveric renal trans...
journal_title:Journal of nephrology
pub_type: 杂志文章
doi:
更新日期:2004-01-01 00:00:00
abstract::A 17-year-old boy was admitted to the hospital twice in a year for 2 episodes of hemolytic uremic syndrome (HUS). During these 2 HUS episodes he had diarrhea, decreased serum complement, decreased total protein and decreased serum albumin concentrations. We suggest that protein-losing enteropathy and hypocomplementemi...
journal_title:Journal of nephrology
pub_type: 杂志文章
doi:
更新日期:2007-03-01 00:00:00
abstract:BACKGROUND:Inadvertent sodium (Na(+)) flux may occur during renal replacement therapy (RRT) in ICU. The objective of this study was to estimate sodium flux during RRT. METHODS:Between September 2011 to December 2012 we studied 60 ICU patients receiving extended daily dialysis (EDD, Fresenius 4008S) or continuous renal...
journal_title:Journal of nephrology
pub_type: 杂志文章
doi:10.1007/s40620-014-0041-8
更新日期:2014-08-01 00:00:00