Genomic and clinical profiling of a national nephrotic syndrome cohort advocates a precision medicine approach to disease management.


:Steroid Resistant Nephrotic Syndrome (SRNS) in children and young adults has differing etiologies with monogenic disease accounting for 2.9-30% in selected series. Using whole exome sequencing we sought to stratify a national population of children with SRNS into monogenic and non-monogenic forms, and further define those groups by detailed phenotypic analysis. Pediatric patients with SRNS were identified via a national United Kingdom Renal Registry. Whole exome sequencing was performed on 187 patients, of which 12% have a positive family history with a focus on the 53 genes currently known to be associated with nephrotic syndrome. Genetic findings were correlated with individual case disease characteristics. Disease causing variants were detected in 26.2% of patients. Most often this occurred in the three most common SRNS-associated genes: NPHS1, NPHS2, and WT1 but also in 14 other genes. The genotype did not always correlate with expected phenotype since mutations in OCRL, COL4A3, and DGKE associated with specific syndromes were detected in patients with isolated renal disease. Analysis by primary/presumed compared with secondary steroid resistance found 30.8% monogenic disease in primary compared with none in secondary SRNS permitting further mechanistic stratification. Genetic SRNS progressed faster to end stage renal failure, with no documented disease recurrence post-transplantation within this cohort. Primary steroid resistance in which no gene mutation was identified had a 47.8% risk of recurrence. In this unbiased pediatric population, whole exome sequencing allowed screening of all current candidate genes. Thus, deep phenotyping combined with whole exome sequencing is an effective tool for early identification of SRNS etiology, yielding an evidence-based algorithm for clinical management.


Kidney Int


Kidney international


Bierzynska A,McCarthy HJ,Soderquest K,Sen ES,Colby E,Ding WY,Nabhan MM,Kerecuk L,Hegde S,Hughes D,Marks S,Feather S,Jones C,Webb NJ,Ognjanovic M,Christian M,Gilbert RD,Sinha MD,Lord GM,Simpson M,Koziell AB,Welsh




Has Abstract


2017-04-01 00:00:00














  • Renal iron handling in the nephrotic syndrome.

    abstract::Renal iron handling was characterized in three experimental models of the nephrotic syndrome: puromycin aminonucleoside, adriamycin and nephrotoxic serum. In adriamycin-induced nephrotic syndrome, which has previously been shown to result from alterations in pore size of the filtration barrier, the transferrin leak wa...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Alfrey AC,Hammond WS

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  • Hypertension and albuminuria in chronic kidney disease mapped to a mouse chromosome 11 locus.

    abstract::Chronic kidney disease (CKD) is a key cause of hypertension and a potent independent risk for cardiovascular disease. Epidemiological studies suggest a strong genetic component determining susceptibility for renal disease and, by inference, the associated cardiovascular risk. With a subtotal nephrectomy model of kidne...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Salzler HR,Griffiths R,Ruiz P,Chi L,Frey C,Marchuk DA,Rockman HA,Le TH

    更新日期:2007-11-01 00:00:00

  • Lead chelation therapy and urate excretion in patients with chronic renal diseases and gout.

    abstract:BACKGROUND:It is known that chronic renal insufficiency (CRI) patients with gout may have subtle lead poisoning. In addition, gout episodes frequently aggravate progressive renal insufficiency because of the use of nephrotoxic drugs and urate deposition. Our study was arranged to evaluate the causal effect of environme...

    journal_title:Kidney international

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Lin JL,Yu CC,Lin-Tan DT,Ho HH

    更新日期:2001-07-01 00:00:00

  • Correlation of clinical and in vitro erythropoietic responses to androgens in renal failure.

    abstract::To assess in vitro erythropoietic cultures as a tool to discriminate between patients whose anemia improves with and those whose anemia fails to improve with androgens, bone marrows of 24 anemic patients receiving maintenance hemodialysis in hormone-depleted plasma clots were cultured. While erythroid colony prolifera...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Kalmanti M,Dainiak N,Martino J,Dewey M,Kulkarni V,Howard D

    更新日期:1982-10-01 00:00:00

  • C1q-binding donor-specific antibody assays help define risk and prognosis in antibody-mediated rejection.

    abstract::Antibody-mediated rejection represents the first cause of graft loss in renal transplant recipients, and it is imperative to identify appropriate tools to enable risk stratification of such patients. Lately, the usefulness of measuring complement-binding anti-human leukocyte antigen (HLA) donor-specific antibodies (DS...

    journal_title:Kidney international

    pub_type: 评论,杂志文章


    authors: Cozzi E,Biancone L

    更新日期:2018-10-01 00:00:00

  • Coordinate regulation of canine glomeruli and adrenal angiotensin receptors by dietary sodium manipulation.

    abstract:BACKGROUND:This study evaluated the effects of dietary sodium manipulation in dogs on the regulation of canine angiotensin receptors (cAT1 and cAT2) in the kidney and adrenal. METHODS:Isolated glomeruli and membranes from renal medulla and the adrenal gland were used in radioligand binding assays from two groups of do...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Zheng W,Ji H,Szabo Z,Brown PR,Yoo SE,Sandberg K

    更新日期:2001-05-01 00:00:00

  • Learning about the practice of peritoneal dialysis.

    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


    authors: Golper TA

    更新日期:2009-07-01 00:00:00

  • Nephron segment and cell-type specific expression of gangliosides in the developing and adult kidney.

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    journal_title:Kidney international

    pub_type: 杂志文章


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    更新日期:1994-01-01 00:00:00

  • Long-term comparison between captopril and nifedipine in the progression of renal insufficiency.

    abstract::To verify the hypothesis that angiotensin-converting enzyme (ACE) inhibitors possess a unique renoprotective effect in progressive chronic renal disease, we decided to compare the effects of an ACE inhibitor and a calcium antagonist on both hypertension and the progression of non-diabetic renal insufficiency in a long...

    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


    authors: Zucchelli P,Zuccalà A,Borghi M,Fusaroli M,Sasdelli M,Stallone C,Sanna G,Gaggi R

    更新日期:1992-08-01 00:00:00

  • Magnetic resonance imaging accurately tracks kidney pathology and heterogeneity in the transition from acute kidney injury to chronic kidney disease.

    abstract::Acute kidney injury (AKI) increases the risk for chronic kidney disease (CKD). However, there are few tools to detect microstructural changes after AKI. Here, cationic ferritin-enhanced magnetic resonance imaging (CFE-MRI) was applied to examine the heterogeneity of kidney pathology in the transition from AKI to CKD. ...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Charlton JR,Xu Y,Wu T,deRonde KA,Hughes JL,Dutta S,Oxley GT,Cwiek A,Cathro HP,Charlton NP,Conaway MR,Baldelomar EJ,Parvin N,Bennett KM

    更新日期:2021-01-01 00:00:00

  • Functional modulation of the mineralocorticoid receptor by cis-diamminedichloroplatinum (II).

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    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Iida T,Makino Y,Okamoto K,Yoshikawa N,Makino I,Nakamura T,Tanaka H

    更新日期:2000-10-01 00:00:00

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    journal_title:Kidney international

    pub_type: 杂志文章


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    更新日期:1993-04-01 00:00:00

  • Role of cyanate in the induction of vascular dysfunction during uremia: more than protein carbamylation?

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    journal_title:Kidney international

    pub_type: 评论,杂志文章


    authors: Hawkins CL

    更新日期:2014-11-01 00:00:00

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    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Lane PH,Steffes MW,Mauer SM

    更新日期:1992-04-01 00:00:00

  • Structure of non-(1-84) PTH fragments secreted by parathyroid glands in primary and secondary hyperparathyroidism.

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    journal_title:Kidney international

    pub_type: 杂志文章


    authors: D'Amour P,Brossard JH,Rousseau L,Nguyen-Yamamoto L,Nassif E,Lazure C,Gauthier D,Lavigne JR,Zahradnik RJ

    更新日期:2005-09-01 00:00:00

  • Malignancy after kidney transplantation: still a challenge.

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    journal_title:Kidney international

    pub_type: 评论,杂志文章


    authors: Bosmans JL,Verpooten GA

    更新日期:2007-06-01 00:00:00

  • The effects of iron dextran on the oxidative stress in cardiovascular tissues of rats with chronic renal failure.

    abstract:BACKGROUND:Redox-active iron can promote oxidative stress and tissue injury by catalyzing hydroxyl radical generation and lipid peroxidation. Intravenous iron preparations are routinely administered in conjunction with erythropoietin to treat anemia in patients with chronic renal failure (CRF), a condition that is mark...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Lim CS,Vaziri ND

    更新日期:2004-05-01 00:00:00

  • Decreased sensitivity to heparin in vitro in steroid-responsive nephrotic syndrome.

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    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Vermylen CG,Levin M,Lanham JG,Hardisty RM,Barratt TM

    更新日期:1987-06-01 00:00:00

  • Regulation of the renal Na-HCO3 cotransporter: VI. Mechanism of the stimulatory effect of protein kinase C.

    abstract::We have previously shown that the activity of the Na-HCO3 cotransporter is stimulated by protein kinase C (PKC) activation, but the mechanism responsible for this effect is not clear. We have shown that cultured proximal tubule cells of the rabbit have DIDS-sensitive Na-HCO3 cotransporter activity as assessed by HCO3-...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Ruiz OS,Wang LJ,Qiu YY,Kear F,Bernardo A,Arruda JA

    更新日期:1996-03-01 00:00:00

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    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Lianos EA,Guglielmi K,Sharma M

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  • Risk factors in idiopathic renal vasculitis and glomerulonephritis.

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    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Wilkowski MJ,Velosa JA,Holley KE,Offord KP,Chu CP,Torres VE,McCarthy JT,Donadio JV Jr,Wagoner RD

    更新日期:1989-12-01 00:00:00

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    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Hörkkö S,Savolainen MJ,Kervinen K,Kesäniemi YA

    更新日期:1992-05-01 00:00:00

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    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Holmes RP,Goodman HO,Assimos DG

    更新日期:2001-01-01 00:00:00

  • Human Bence Jones protein toxicity in rat proximal tubule epithelium in vivo.

    abstract::To investigate the direct toxicity of human Bence Jones protein (BJP), individual nephrons of male Sprague-Dawley rats were perfused in vivo at 20 nl/min with an artificial tubule fluid (ATF) that contained no protein, a human kappa BJP (5 g/dl), or bovine serum albumin (5 g/dl), and proximal convoluted tubule functio...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Sanders PW,Herrera GA,Galla JH

    更新日期:1987-12-01 00:00:00

  • Urine citrate excretion as a marker of acid retention in patients with chronic kidney disease without overt metabolic acidosis.

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    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Goraya N,Simoni J,Sager LN,Madias NE,Wesson DE

    更新日期:2019-05-01 00:00:00

  • Beneficial impact of spironolactone in diabetic nephropathy.

    abstract:BACKGROUND:Aldosterone has been suggested to play a role in the initiation and progression of diabetic nephropathy. Currently recommended treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers [renin-angiotensin system (RAS) blockade] does not suppress circulating aldosterone ...

    journal_title:Kidney international

    pub_type: 杂志文章,随机对照试验


    authors: Schjoedt KJ,Rossing K,Juhl TR,Boomsma F,Rossing P,Tarnow L,Parving HH

    更新日期:2005-12-01 00:00:00

  • Hereditary systemic amyloidosis associated with a new apolipoprotein AII stop codon mutation Stop78Arg.

    abstract:UNLABELLED:Hereditary systemic amyloidosis associated with a new apolipoprotein AII stop codon mutation Stop78Arg. BACKGROUND:Mutations in the gene for apolipoprotein AII (apoAII) have recently been found to cause hereditary renal amyloidosis. In each case amyloid deposition has been associated with a peptide extensio...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Yazaki M,Liepnieks JJ,Barats MS,Cohen AH,Benson MD

    更新日期:2003-07-01 00:00:00

  • The soluble urokinase receptor is not a clinical marker for focal segmental glomerulosclerosis.

    abstract::The soluble urokinase receptor (suPAR) promotes proteinuria and induces focal segmental glomerulosclerosis (FSGS)-like lesions in mice. A serum suPAR concentration cutoff of 3000 pg/ml has been proposed as a clinical biomarker for patients with FSGS. Interestingly, several studies in patients with glomerulopathy found...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Meijers B,Maas RJ,Sprangers B,Claes K,Poesen R,Bammens B,Naesens M,Deegens JK,Dietrich R,Storr M,Wetzels JF,Evenepoel P,Kuypers D

    更新日期:2014-03-01 00:00:00

  • Crystalluria: a clinically useful investigation in children with primary hyperoxaluria post-transplantation.

    abstract::Primary hyperoxaluria type I (PH I) is a congenital error of metabolism that can be manifested by an increased oxalate production, and ultimately result in kidney failure. After a combined liver/kidney transplantation, children with PH I have persistent excretion of oxalate that causes crystal formation in the urinary...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Jouvet P,Priqueler L,Gagnadoux MF,Jan D,Beringer A,Lacaille F,Revillon Y,Broyer M,Daudon M

    更新日期:1998-05-01 00:00:00

  • Association between residence location and likelihood of kidney transplantation in Aboriginal patients treated with dialysis in Canada.

    abstract::For reasons that are not well understood, Aboriginal people with end-stage renal disease (ESRD) have lower rates of kidney transplantation. We hypothesized that distance between residence location and the closest transplant center was greater in Aboriginal dialysis patients and would partially explain the lower rate o...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Tonelli M,Hemmelgarn B,Kim AK,Bertazzon S,Klarenbach S,Manns B,Wiebe N,Culleton B,Gill JS,Alberta Kidney Disease Network.

    更新日期:2006-09-01 00:00:00