Chronic kidney disease

Nature Reviews Disease Primers, Journal Year: 2017, Volume and Issue: 3(1)

Published: Nov. 22, 2017

Language: Английский

Podocytopathies

Nature Reviews Disease Primers, Journal Year: 2020, Volume and Issue: 6(1)

Published: Aug. 13, 2020

Language: Английский

Structural and Functional Changes in Human Kidneys with Healthy Aging

Journal of the American Society of Nephrology, Journal Year: 2017, Volume and Issue: 28(10), P. 2838 - 2844

Published: Aug. 8, 2017

Aging is associated with significant changes in structure and function of the kidney, even absence age-related comorbidities. On macrostructural level, kidney cortical volume decreases, surface roughness increases, number size simple renal cysts increase age. microstructural histologic signs nephrosclerosis (arteriosclerosis/arteriolosclerosis, global glomerulosclerosis, interstitial fibrosis, tubular atrophy) all The decline nephron accompanied by a comparable reduction measured whole-kidney GFR. However, single-nephron GFR remains relatively constant healthy aging as does glomerular volume. Only when glomerulosclerosis arteriosclerosis exceed that expected for age there an In albuminuria, corresponding CKD (defined eGFR<60 ml/min per 1.73 m2) has been shown to associate very modest no age-standardized mortality risk or ESRD. These findings raise question whether disease labeling appropriate. also emphasize need different management approach many elderly individuals considered have current criteria.

Language: Английский

Single-Nephron Glomerular Filtration Rate in Healthy Adults

New England Journal of Medicine, Journal Year: 2017, Volume and Issue: 376(24), P. 2349 - 2357

Published: June 14, 2017

The glomerular filtration rate (GFR) assesses the function of all nephrons, and single-nephron GFR individual nephrons. How relates to demographic clinical characteristics kidney-biopsy findings in humans is unknown.We identified 1388 living kidney donors at Mayo Clinic Cleveland who underwent a computed tomographic (CT) scan with use contrast material an iothalamate-based measurement during donor evaluation biopsy donation. mean was calculated as divided by number nephrons (calculated cortical volume both kidneys assessed on CT times biopsy-determined density). Demographic were correlated GFR.A total 58% women, (±SD) age 44±12 years. 115±24 ml per minute, 860,000±370,000 kidney, 80±40 nl minute. did not vary significantly according (among <70 years age), sex, or height ≤190 cm tall). A higher independently associated larger more glomerulosclerosis arteriosclerosis than would be expected for age. 190 cm, obesity, family history end-stage renal disease.Among healthy adult donors, fairly constant regard age, (if cm). certain risk factors chronic disease findings. (Funded National Institute Diabetes Digestive Kidney Diseases.).

Language: Английский

Differentiating Primary, Genetic, and Secondary FSGS in Adults: A Clinicopathologic Approach

Journal of the American Society of Nephrology, Journal Year: 2018, Volume and Issue: 29(3), P. 759 - 774

Published: Jan. 10, 2018

FSGS describes a renal histologic lesion with diverse causes and pathogenicities that are linked by podocyte injury depletion. Subclasses of include primary, genetic, secondary forms, the latter comprising maladaptive, viral, drug-induced FSGS. Despite sharing certain clinical features, these subclasses differ noticeably in management prognosis. Without an accepted nongenetic biomarker discriminates among types, classification patients is often challenging. This review summarizes including onset severity proteinuria as well presence nephrotic syndrome, may aid identifying specific subtype. The characterized segmental sclerosis must be differentiated from nonspecific focal global glomerulosclerosis. No light microscopic features pathognomonic for particular subcategory. characteristics foot process effacement on electron microscopy, while helpful discriminating between primary maladaptive FSGS, little utility detecting genetic forms When cannot classified clinicopathologic assessment, analysis should offered. Next generation DNA sequencing enables cost-effective screening multiple genes simultaneously, but determining pathogenicity detected variant A more systematic evaluation patients, suggested herein, will likely improve therapeutic outcomes design future trials

Language: Английский

Management and treatment of glomerular diseases (part 1): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Kidney International, Journal Year: 2019, Volume and Issue: 95(2), P. 268 - 280

Published: Jan. 18, 2019

The Kidney Disease: Improving Global Outcomes (KDIGO) initiative organized a Controversies Conference on glomerular diseases in November 2017. conference focused the 2012 KDIGO guideline with aim of identifying new insights into nomenclature, pathogenesis, diagnostic work-up, and, particular, therapy since guideline's publication. It was consensus group that most recommendations, particular those dealing therapy, will need to be revisited by guideline-updating Work Group. This report covers general management disease, IgA nephropathy, and membranous nephropathy. published its first 2012.1Kidney Glomerulonephritis GroupKDIGO clinical practice for glomerulonephritis.Kidney Int Suppl. 2012; 2: 139-274Google Scholar Given enormous advances understanding pathogenesis diseases, identification biomarkers, emerging therapies, about 100 experts from various disciplines (nephrology, pathology, rheumatology, pediatrics) organizations (academia, pharmaceutical industry) convened 17–19, Through plenary small discussions, aimed evaluate controversies work-up future needs research, critical assessment existing recommendations. 2 reports diseases. In addition, this addresses common forms glomerulonephritis (GN), namely nephropathy (IgAN) Primary podocytopathies, complement-mediated lupus nephritis, antineutrophil cytoplasmic antibody–associated monoclonal gammopathies renal significance covered second report. These summaries lay basis updating process began August 2018. section consider newer concepts principles disorders. Disease-specific issues, applications, or exceptions these statements discussed within each individual disease sections. Additional broad-based may found chapter Clinical Practice Guideline Glomerulonephritis.1Kidney kidney biopsy remains cornerstone evaluation disease.2Sethi S. D'Agati V.D. Nast C.C. et al.A proposal standardized grading chronic changes native specimens.Kidney Int. 2017; 91: 787-789Google Scholar, 3D'Agati Mengel M. rise pathology nephrology: structure illuminates function.Am J Dis. 2013; 61: 1016-1025Google very few specific circumstances such as childhood steroid-sensitive nephrotic syndrome, diagnosis treatment are often done without biopsy. adults approach is uncommon but considered cases. For example, patients who have normal function, acute onset positive anti-phospholipase A2 receptor (PLA2R) antibodies likely Treatment could initiated if had high risk procedural complications, care must taken other emulate all features.4Larsen C.P. Messias N.C. Silva F.G. al.Determination primary versus secondary glomerulopathy utilizing phospholipase staining biopsies.Mod Pathol. 26: 709-715Google 5Dai H. Zhang He Y. Diagnostic accuracy PLA2R autoantibodies differentiation idiopathic nephropathy: an updated meta-analysis.Sci Rep. 2015; 5: 8803Google tissue also assessing degree histologic activity chronicity identify unexpected features interstitial injury, crescents, factors might significantly impact management. should interpreted context ethnicity, age, hypertension, modify background histology. instance, "normal" range age-related focal segmental glomerulosclerosis population allow better estimate extent biopsy.6Hodgin J.B. Bitzer Wickman L. al.Glomerular aging global glomerulosclerosis: podometric perspective.J Am Soc Nephrol. 3162-3178Google Application modifiers, considered. value expand near term. taking more system-related enhance providing information important diagnosis, prognosis, treatment. trials failures suggesting variations between individuals molecular pathways driving progression despite similar histopathology. To develop targeted necessary require focus mechanisms operative at level rather than relying solely standard findings. ties concept immunologic remission.5Dai 7Beck Jr., L.H. Fervenza F.C. Beck D.M. al.Rituximab-induced depletion anti-PLA2R predicts response nephropathy.J 2011; 22: 1543-1550Google 8De Vriese A.S. Glassock R.J. Nath K.A. serology-based 28: 421-430Google electron microscopy every controversial. can some cases, differentiate immunologically mediated adaptive variants.9Sethi Focal towards practicing nephrologist.Nephrol Dial Transplant. 30: 375-384Google worldwide difficult, it possibly leveraged preservation amount judged management, sent reference laboratory evaluation. Most associated significant proteinuria. Although ratios albumin-to-creatinine protein-to-creatinine (PCR) random spot urines commonly used, recent data highlight poor agreement 24-hour urine protein measurements.10Hogan M.C. Reich H.N. Nelson P.J. al.The relatively correlation excretion biopsy-proven diseases.Kidney 2016; 90: 1080-1089Google ratio PCR helpful they not sufficiently accurate when therapeutic decisions using high-risk medications being made proteinuria.11Reich Troyanov Scholey J.W. al.Remission proteinuria improves prognosis 2007; 18: 3177-3183Google 12Lv J. Wong M.G. al.Effect oral methylprednisolone outcomes TESTING randomized trial.JAMA. 318: 432-442Google measured. Importantly, intended collection least 50% complete has been shown accurately reflect proteinuria.13Hebert L.A. Birmingham D.J. Shidham G. al.Random protein/creatinine unreliable estimating systemic erythematosus nephritis patients.Nephron Clin Pract. 2009; 113: c177-c182Google young children, obtaining usually possible preferred means assess Monitoring serum albumin levels represents valuable tool indirectly gold excretory function inulin isotopic clearance techniques, expensive operator expertise. Newer, techniques measure filtration rate (GFR) evolving.14Rizk D.V. Meier D. Sandoval R.M. novel method rapid bedside measurement GFR.J 2018; 29: 1609-1613Google Presently, Chronic Disease Epidemiology Collaboration's (CKD-EPI) equation GFR used instead.15Ix J.H. Wassel C.L. Stevens al.Equations creatinine rate: CKD epidemiology collaboration.Clin 6: 184-191Google Formulas developed children.16Gao A. Cachat F. Faouzi al.Comparison children revised Schwartz formula generalized formula.Kidney 83: 524-530Google 17Schwartz G.J. D.F. Measurement estimation adolescents.Clin 4: 1832-1843Google However, estimated (eGFR) equations validated patient populations. high-grade proteinuria, majority studies still use collections clearance. Errors related measurements under conditions induce up errors measurement.18Branten A.J. Vervoort Wetzels J.F. Serum marker syndrome.Nephrol 2005; 20: 707-711Google 19Stevens Levey Measured confirmatory test 2305-2313Google 20Inker Tonelli Hemmelgarn B.R. concurrent complications categorization systems.Am 59: 372-381Google methods partially compensated frequent longitudinal data-smoothing techniques.21Tang L.L. Liu Chen Z. al.Nonparametric ROC summary statistics correlated data.Stat Med. 32: 2209-2220Google A simple, reliable, inexpensive biomarker wanting. Macro- microhematuria almost disorders red cell casts provide clues nephritic IgAN. Qualitatively, routine dipstick distinguish presence absence microhematuria, capacity quantitate hematuria pitfalls, including timing examination, concentration, preparation pellet, pH urine, expertise examiner. disappearance hematuria, however, remission IgAN antibody vasculitis.22Geetha Seo P. Ellis C. al.Persistent microscopic vessel vasculitis remission: findings biopsy.J Rheumatol. 39: 1413-1417Google 23Sevillano A.M. Gutierrez E. Yuste survival 3089-3099Google Regulatory agencies grant approval drugs GN based classic outcome, end-stage (ESKD) (or reduction eGFR), and/or mortality negative outcomes. Recent collaborations among US Food Drug Administration, industry, members nephrology organizations, umbrella organization, Health Initiative, developing alternative surrogate endpoints drug approval. meeting culminated decision 40% eGFR serve endpoint, earlier needed rare diseases.24Levey Inker Matsushita K. al.GFR decline end point CKD: scientific workshop sponsored National Foundation Administration.Am 2014; 64: 821-835Google suggest endpoint partial accelerated program United States.25Thompson Cattran D.C. Blank al.Complete points 2930-2937Google Both supported statistical prospective quantitation benefit duration patient.26Cattran Kim E.D. al.Membranous quantifying outcome.J 995-1003Google Initiative currently evaluating nephritis. futility "point no return" defined low eGFR, < 30 ml/min per 1.73 m2 shows irreversible changes.1Kidney Noninvasive whole chronicity/fibrosis ready application.27Morrell G.R. J.L. Lee V.S. Magnetic resonance imaging fibrotic kidney.J 2564-2570Google Currently, change single cross-sectional defining futility. Additionally, age overall wellness determining question extends trials. Futility criteria exclude thought outweigh gain patients. Therefore, many miss opportunity participate trials, complicating attainment sample size generalizability results. engagement trial eligibility. If treating physician thinks reasonable their fully informed, were less rigid. followed practice. controversial, become relevant low-risk treatments available. Quality life health components increasingly regulatory worth treatment.1Kidney patient-related outcome evolving, standards guidelines do yet exist. addition well-established persistent poorly controlled hypertension diabetes, smoking, widespread cardiovascular disease,28Hebert Wilmer W.A. Falkenhain M.E. al.Renoprotection: one therapies?.Kidney 2001; 1211-1226Google evidence supports prematurity having nephron endowment potentially limiting reserve increasing (Table 1).29Bertram Douglas-Denton R.N. Diouf B. al.Human number: implications disease.Pediatr 1529-1533Google approximated birth weight, readily available, low-cost demographic. Its speculative, basic affect diseases.Table 1Established diseaseRisk progressive loss GFREmerging GFR•Persistent proteinuria•Poorly hypertension•Poorly diabetes mellitus•Smoking•Widespread disease•Use nephrotoxic drugs•Prematurity (low weight) reasons number29Bertram Scholar•Low-sleep (e.g., restless legs sleep apnea)30Ricardo A.C. Goh V. al.Association duration, symptoms, disease.Kidney 866-873Google Scholar•Obesity31Morales Valero M.A. Leon al.Beneficial effects weight overweight proteinuric nephropathies.Am 2003; 41: 319-327Google 32Afshinnia Wilt T.J. Duval al.Weight proteinuria: systematic review comparative cohorts.Nephrol 2010; 25: 1173-1183Google 33Kittiskulnam Kanjanabuch T. Tangmanjitjaroen beneficial immunoglobulin trial.J Ren Nutr. 24: 200-207Google Scholar•Gender?34Cattran Beanlands H.J. sex glomerulonephritis.Nephrol 2008; 23: 2247-2253Google ScholarGFR, rate. Open table tab GFR, Another recently factor hygiene. From Nutrition Examination Survey population, low-sleep apnea) all-cause mortality. Extrapolation seems modifiable applied broadly patients.30Ricardo Weight obese diseases.31Morales Small studies, focusing diet bypass surgery, short-term benefits. improvement intriguing additions approaches economical, widely applicable, foster engagement. Sex another issue part stratification GN. data, different rates driven category, blood pressure (BP), severity sex.34Cattran Genetic testing rapidly evolved role expanded include only confirming diagnoses, establishing inheritance patterns, differentiating heterogeneous disorders, appropriate treatment, guiding family planning, cause unexplained familial expected susceptibility progression. Currently cost unclear limit genetic testing.35Sampson Hodgin Kretzler Defining syndrome integrative genomics perspective.Pediatr 51-63Google 36Preston R, Stuart HM, Lennon R. steroid-resistant syndrome: why, who, how? [e-pub ahead print]. Pediatr https://doi.org/10.1007/s00467-017-3838-6. Accessed December 15, 2018.Google Hypertension control crucial controversy remains, support BP target 125/75 mm Hg >1 g/d. Critical resistant careful patient's dietary sodium intake. Educating how interpret food labels feedback intake estimates effective strategies.37Agarwal Resistant neglected antihypertensive: restriction.Nephrol 27: 4041-4045Google 38Bibbins-Domingo Chertow G.M. Coxson P.G. al.Projected effect salt reductions disease.N Engl 362: 590-599Google Sodium restriction lower BP, antiproteinuric renin–angiotensin system (RAS) blockers. Institute Medicine recommends <1500 mg/d (65 mmol/d), which 75% average North American There clear optimal children. Proteinuria goal virtually main through RAS blockade. An area whether angiotensin-converting enzyme inhibitors angiotensin blockers alone, dual combination aldosterone antagonist. Previously, hyperkalemia injury outweighed benefits indicate monitoring, safe.39Voskamp P.W.M. Dekker F.W. van Diepen compared renin-angiotensin blockade replacement death predialysis patients: PREPARE-2 study.J Hypertens. 11: 635-643Google Nonetheless, clear.39Voskamp practical ameliorating risks due blockers, particularly "sick day instructions" withhold decrease dose during periods volume occur, vomiting diarrhea. Aldosterone reduces heart failure albuminuria.40Joseph J.J. Echouffo-Tcheugui Kalyani R.R. al.Aldosterone, renin, events, African Americans: Jackson Heart Study.JACC Fail. 642-651Google 41Petrykiv S.I. Laverman G.D. Persson al.Pooled analysis multiple crossover optimize renin-angiotensin-aldosterone intervention.Clin 12: 1804-1813Google 42Antlanger Bernhofer Kovarik al.Effects direct renin inhibition II profiles non-diabetic disease.Ann 49: 525-533Google absolute risk-benefit unclear. sodium-glucose transport proteins (SGLT2) offer strategy. study, SGLT2 inhibitor dapagliflozin did hemodynamic attenuate nondiabetic humans glomerulosclerosis, because downregulation expression glomerulosclerosis.43Rajasekeran Hladunewich al.Dapagliflozin combined human-rodent pilot study.Am Physiol Renal Physiol. 314: F412-F422Google Several large investigating Study Protection With Empagliflozin [EMPA-KIDNEY], NCT03594110; Effects Dapagliflozin Nondiabetic Patients [DIAMOND], NCT03190694; Evaluate Effect Cardiovascular Mortality [Dapa-CKD], NCT03036150). vascular seen includes GN, worse others.44Markossian Burge N. Ling al.Controversies regarding lipid statin CKD.Am 67: 965-977Google 45Lee Derebail V.K. Kshirsagar A.V. al.Patients events.Kidney 89: 1111-1118Google traditionally statins treat hyperlipidemia effective, values achieved, especially era low-density lipoprotein levels. Novel powerful agents proprotein convertase subtilisin/kexin type 9 evolocumab, alirocumab) studied population.46Sabatine M.S. Giugliano R.P. Keech al.Evolocumab 376: 1713-1722Google Evidence lipid-lowering quality explored given longevity.47Kotur-Stevuljevic Peco-Antic Spasic al.Hyperlipidemia, oxidative stress, intima media thickness 295-303Google contrast statins, well established.48Haynes Lewis Emberson lowering LDL cholesterol disease.J 1825-1833Google Concerning prophylactic anticoagulation patients, thrombotic aids available online (www.med.unc.edu/gntools).49Lee Biddle A.K. Lionaki al.Personalized nephropathy.Kidney 85: 1412-1420Google 50Barbour S.J. Greenwald Djurdjev O. al.Disease-specific venous thromboembolic events increased 81: 190-195Google Whether non-vitamin-K antagonist anticoagulants safely demonstrated above m2. severe anticoagulant metabolism further study.51Stamellou Floege atrial fibrillation.Nephrol 33: 1683-1689Google infection

Language: Английский

An endoplasmic reticulum stress-regulated lncRNA hosting a microRNA megacluster induces early features of diabetic nephropathy

Nature Communications, Journal Year: 2016, Volume and Issue: 7(1)

Published: Sept. 30, 2016

Abstract It is important to find better treatments for diabetic nephropathy (DN), a debilitating renal complication. Targeting early features of DN, including extracellular matrix accumulation (ECM) and glomerular hypertrophy, can prevent disease progression. Here we show that megacluster nearly 40 microRNAs their host long non-coding RNA transcript (lnc-MGC) are coordinately increased in the glomeruli mouse models mesangial cells treated with transforming growth factor-β1 (TGF- β1) or high glucose. Lnc-MGC regulated by an endoplasmic reticulum (ER) stress-related transcription factor, CHOP. Cluster lnc-MGC decreased Chop −/− mice showed protection from DN. Target genes have functions related protein synthesis ER stress. A chemically modified oligonucleotide targeting inhibits cluster microRNAs, ECM hypertrophy mice. Relevance human DN also demonstrated. These results demonstrate translational implications controlling

Language: Английский

Digital pathology and computational image analysis in nephropathology

Nature Reviews Nephrology, Journal Year: 2020, Volume and Issue: 16(11), P. 669 - 685

Published: Aug. 26, 2020

Language: Английский

Biomarkers of aging

Science China Life Sciences, Journal Year: 2023, Volume and Issue: 66(5), P. 893 - 1066

Published: April 11, 2023

Language: Английский

Molecular mechanisms of renal aging

Kidney International, Journal Year: 2017, Volume and Issue: 92(3), P. 569 - 579

Published: July 18, 2017

Language: Английский