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Nephrotic syndrome, type 6(NPHS6)

MedGen UID:
481730
Concept ID:
C3280100
Disease or Syndrome
Synonym: NPHS6
 
Gene (location): PTPRO (12p12.3)
 
Monarch Initiative: MONDO:0013619
OMIM®: 614196

Definition

The nephrotic syndrome refers to a genetically heterogeneous group of disorders characterized by proteinuria, hypoalbuminemia, and edema, resulting in end-stage kidney disease if untreated. Inherited defects in podocyte structure and function have been observed in some children with the steroid-resistant subtype of nephrotic syndrome (summary by Ozaltin et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300). [from OMIM]

Clinical features

From HPO
Focal segmental glomerulosclerosis
MedGen UID:
4904
Concept ID:
C0017668
Disease or Syndrome
Segmental accumulation of scar tissue in individual (but not all) glomeruli.
Nephrotic syndrome
MedGen UID:
10308
Concept ID:
C0027726
Disease or Syndrome
Nephrotic syndrome is a collection of findings resulting from glomerular dysfunction with an increase in glomerular capillary wall permeability associated with pronounced proteinuria. Nephrotic syndrome refers to the constellation of clinical findings that result from severe renal loss of protein, with Proteinuria and hypoalbuminemia, edema, and hyperlipidemia.
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
Increased levels of protein in the urine.
Tubulointerstitial fibrosis
MedGen UID:
370652
Concept ID:
C1969372
Disease or Syndrome
A progressive detrimental connective tissue deposition (fibrosis) on the kidney parenchyma involving the tubules and interstitial tissue of the kidney. Tubulointerstitial injury in the kidney is complex, involving a number of independent and overlapping cellular and molecular pathways, with renal interstitial fibrosis and tubular atrophy (IF/TA) as the final common pathway. However, IF and TA are separable, as shown by the profound TA in renal artery stenosis, which characteristically has little or no fibrosis (or inflammation). For new annotations it is preferable to annotate to the specific HPO terms for Renal interstitial fibrosis and/or Renal tubular atrophy.
Stage 5 chronic kidney disease
MedGen UID:
384526
Concept ID:
C2316810
Disease or Syndrome
A degree of kidney failure severe enough to require dialysis or kidney transplantation for survival characterized by a severe reduction in glomerular filtration rate (less than 15 ml/min/1.73 m2) and other manifestations including increased serum creatinine.
Lipoid nephrosis
MedGen UID:
10307
Concept ID:
C0027721
Disease or Syndrome
The presence of minimal changes visible by light microscopy but flattened and fused podocyte foot processes on electron microscopy in a person with nephrotic range proteinuria.
Edema
MedGen UID:
4451
Concept ID:
C0013604
Pathologic Function
An abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body.
Hypoalbuminemia
MedGen UID:
68694
Concept ID:
C0239981
Finding
Reduction in the concentration of albumin in the blood.

Professional guidelines

PubMed

Dufek S, Holtta T, Trautmann A, Ylinen E, Alpay H, Ariceta G, Aufricht C, Bacchetta J, Bakkaloglu SA, Bayazit A, Cicek RY, Dursun I, Duzova A, Ekim M, Iancu D, Jankauskiene A, Klaus G, Paglialonga F, Pasini A, Printza N, Said Conti V, do Sameiro Faria M, Schmitt CP, Stefanidis CJ, Verrina E, Vidal E, Vondrak K, Webb H, Zampetoglou A, Bockenhauer D, Edefonti A, Shroff R
Nephrol Dial Transplant 2019 Aug 1;34(8):1369-1377. doi: 10.1093/ndt/gfy165. PMID: 30215773
Chiou YH, Wang LY, Wang TH, Huang SP
Pediatr Nephrol 2012 Sep;27(9):1511-7. Epub 2012 May 20 doi: 10.1007/s00467-012-2182-0. PMID: 22610055
Holmberg C, Antikainen M, Rönnholm K, Ala Houhala M, Jalanko H
Pediatr Nephrol 1995 Feb;9(1):87-93. doi: 10.1007/BF00858984. PMID: 7742232

Recent clinical studies

Etiology

Sethi S, Madden B, Debiec H, Morelle J, Charlesworth MC, Gross L, Negron V, Buob D, Chaudhry S, Jadoul M, Fervenza FC, Ronco P
J Am Soc Nephrol 2021 May 3;32(5):1249-1261. Epub 2021 Apr 8 doi: 10.1681/ASN.2020081165. PMID: 33833079Free PMC Article
van de Logt AE, Fresquet M, Wetzels JF, Brenchley P
Kidney Int 2019 Dec;96(6):1292-1302. Epub 2019 Aug 12 doi: 10.1016/j.kint.2019.07.014. PMID: 31611068
Sethi S, Madden BJ, Debiec H, Charlesworth MC, Gross L, Ravindran A, Hummel AM, Specks U, Fervenza FC, Ronco P
J Am Soc Nephrol 2019 Jun;30(6):1123-1136. Epub 2019 May 6 doi: 10.1681/ASN.2018080852. PMID: 31061139Free PMC Article
Feng M, Yuan W, Zhang R, Fu P, Wu T
Cochrane Database Syst Rev 2013 Jun 5;2013(6):CD006335. doi: 10.1002/14651858.CD006335.pub3. PMID: 23740567Free PMC Article
Lloyd JK
Br Heart J 1975 Feb;37(2):105-14. doi: 10.1136/hrt.37.2.105. PMID: 164201Free PMC Article

Diagnosis

Sealfon R, Mariani L, Avila-Casado C, Nair V, Menon R, Funk J, Wong A, Lerner G, Hayashi N, Troyanskaya O, Kretzler M, Beck LH Jr
J Am Soc Nephrol 2022 Jun;33(6):1208-1221. Epub 2022 Apr 27 doi: 10.1681/ASN.2021060784. PMID: 35477557Free PMC Article
Gertz MA, Dispenzieri A
JAMA 2020 Jul 7;324(1):79-89. doi: 10.1001/jama.2020.5493. PMID: 32633805
AlYousef A, AlSahow A, AlHelal B, Alqallaf A, Abdallah E, Abdellatif M, Nawar H, Elmahalawy R
BMC Nephrol 2020 May 18;21(1):186. doi: 10.1186/s12882-020-01836-3. PMID: 32423387Free PMC Article
van de Logt AE, Fresquet M, Wetzels JF, Brenchley P
Kidney Int 2019 Dec;96(6):1292-1302. Epub 2019 Aug 12 doi: 10.1016/j.kint.2019.07.014. PMID: 31611068
Lloyd JK
Br Heart J 1975 Feb;37(2):105-14. doi: 10.1136/hrt.37.2.105. PMID: 164201Free PMC Article

Therapy

Gertz MA, Dispenzieri A
JAMA 2020 Jul 7;324(1):79-89. doi: 10.1001/jama.2020.5493. PMID: 32633805
Mayer U, Schmitz J, Bräsen JH, Pape L
Pediatr Nephrol 2020 May;35(5):829-842. Epub 2020 Feb 12 doi: 10.1007/s00467-019-04436-y. PMID: 32052153Free PMC Article
Feng M, Yuan W, Zhang R, Fu P, Wu T
Cochrane Database Syst Rev 2013 Jun 5;2013(6):CD006335. doi: 10.1002/14651858.CD006335.pub3. PMID: 23740567Free PMC Article
Yuan W, Wang J, Wu T
Cochrane Database Syst Rev 2008 Apr 16;(2):CD006335. doi: 10.1002/14651858.CD006335.pub2. PMID: 18425948
Lloyd JK
Br Heart J 1975 Feb;37(2):105-14. doi: 10.1136/hrt.37.2.105. PMID: 164201Free PMC Article

Prognosis

Sealfon R, Mariani L, Avila-Casado C, Nair V, Menon R, Funk J, Wong A, Lerner G, Hayashi N, Troyanskaya O, Kretzler M, Beck LH Jr
J Am Soc Nephrol 2022 Jun;33(6):1208-1221. Epub 2022 Apr 27 doi: 10.1681/ASN.2021060784. PMID: 35477557Free PMC Article
Gertz MA, Dispenzieri A
JAMA 2020 Jul 7;324(1):79-89. doi: 10.1001/jama.2020.5493. PMID: 32633805
AlYousef A, AlSahow A, AlHelal B, Alqallaf A, Abdallah E, Abdellatif M, Nawar H, Elmahalawy R
BMC Nephrol 2020 May 18;21(1):186. doi: 10.1186/s12882-020-01836-3. PMID: 32423387Free PMC Article
van de Logt AE, Fresquet M, Wetzels JF, Brenchley P
Kidney Int 2019 Dec;96(6):1292-1302. Epub 2019 Aug 12 doi: 10.1016/j.kint.2019.07.014. PMID: 31611068
Sethi S, Madden BJ, Debiec H, Charlesworth MC, Gross L, Ravindran A, Hummel AM, Specks U, Fervenza FC, Ronco P
J Am Soc Nephrol 2019 Jun;30(6):1123-1136. Epub 2019 May 6 doi: 10.1681/ASN.2018080852. PMID: 31061139Free PMC Article

Clinical prediction guides

Sealfon R, Mariani L, Avila-Casado C, Nair V, Menon R, Funk J, Wong A, Lerner G, Hayashi N, Troyanskaya O, Kretzler M, Beck LH Jr
J Am Soc Nephrol 2022 Jun;33(6):1208-1221. Epub 2022 Apr 27 doi: 10.1681/ASN.2021060784. PMID: 35477557Free PMC Article
AlYousef A, AlSahow A, AlHelal B, Alqallaf A, Abdallah E, Abdellatif M, Nawar H, Elmahalawy R
BMC Nephrol 2020 May 18;21(1):186. doi: 10.1186/s12882-020-01836-3. PMID: 32423387Free PMC Article
Li LZ, Hu Y, Ai SL, Cheng L, Liu J, Morris E, Li Y, Gou SJ, Fu P
Sci Rep 2019 Apr 23;9(1):6421. doi: 10.1038/s41598-019-42905-4. PMID: 31015507Free PMC Article
Dryer SE, Roshanravan H, Kim EY
Biochim Biophys Acta Mol Basis Dis 2019 Jun 1;1865(6):1041-1066. Epub 2019 Apr 4 doi: 10.1016/j.bbadis.2019.04.001. PMID: 30953689
Kronenberg F, Utermann G, Dieplinger H
Am J Kidney Dis 1996 Jan;27(1):1-25. doi: 10.1016/s0272-6386(96)90026-8. PMID: 8546123

Recent systematic reviews

Zhang J, Fan Z, Wang P, Zhang AH
Kidney Blood Press Res 2023;48(1):102-113. Epub 2023 Jan 31 doi: 10.1159/000529415. PMID: 36720217
Pournasiri Z, Madani A, Nazarpack F, Sayer JA, Chavoshzadeh Z, Nili F, Tran P, Saba JD, Jamee M
World J Pediatr 2023 May;19(5):425-437. Epub 2022 Nov 12 doi: 10.1007/s12519-022-00615-4. PMID: 36371483
Gertz MA, Dispenzieri A
JAMA 2020 Jul 7;324(1):79-89. doi: 10.1001/jama.2020.5493. PMID: 32633805
Feng M, Yuan W, Zhang R, Fu P, Wu T
Cochrane Database Syst Rev 2013 Jun 5;2013(6):CD006335. doi: 10.1002/14651858.CD006335.pub3. PMID: 23740567Free PMC Article
Yuan W, Wang J, Wu T
Cochrane Database Syst Rev 2008 Apr 16;(2):CD006335. doi: 10.1002/14651858.CD006335.pub2. PMID: 18425948

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