PMID- 11703607
OWN - NLM
STAT- MEDLINE
DCOM- 20020110
LR  - 20220330
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 60
IP  - 5
DP  - 2001 Nov
TI  - Glomerular protein sieving and implications for renal failure in Fanconi 
      syndrome.
PG  - 1885-92
AB  - BACKGROUND: Glomerular sieving coefficients (GSCs) of proteins have been measured 
      extensively in animals but not humans. We have studied the proteinuria of Fanconi 
      syndrome, a "knock-out" of renal tubular protein reabsorption, to estimate GSCs 
      and detect potential contributors to development of renal failure. METHODS: 
      Immunoassay of proteins and polypeptides in serum and urine of patients with 
      early Dent's disease (mean GFR = 83 mL/min, range 60 to 101, N = 5), Lowe's 
      syndrome (N = 3), and ADIF (N = 2) were used. RESULTS: Twenty-one proteins, 
      ranging in mass from insulin (5.1 kD) and parathyroid hormone (PTH; 9.4 kD) to 
      transferrin (78 kD) and intact IgG (160 kD), were present in Fanconi urine at> 6 
      to 1000-fold normal. A simple model assuming complete "knock-out" of the reuptake 
      of each protein filtered normally by the glomerulus was applied to protein 
      excretion by Dent's patients. GSCs were estimated for 12 plasma proteins, 
      including albumin (7.7 +/- 0.9 x 10-5) and IgG (4.2 +/- 0.28 x 10-5; mean +/- 
      SEM). We calculated the albumin concentration in normal glomerular filtrate to be 
      3.5 +/- 0.41 mg/L (53 +/- 6.4 nmol/L), consistent with studies in rat and dog. 
      CONCLUSIONS: To our knowledge, this study provides the first estimates of human 
      in vivo GSCs. Our model explains why tubular proteinuria of Fanconi syndrome 
      includes proteins of mass of albumin and above as well as low-molecular-weight 
      proteins, and further characterizes the endocytic pathway(s) believed defective 
      in these syndromes. High urinary concentrations of potentially bioactive hormones 
      such as PTH, insulin, IGF-1 and the chemokine monocyte chemoattractant protein-1 
      (MCP-1), were found; their presence in tubular fluid may contribute to the 
      hypercalciuria, interstitial fibrosis, and the progressive renal failure of 
      Fanconi syndromes.
FAU - Norden, A G
AU  - Norden AG
AD  - Department of Clinical Biochemistry, Box 232, Addenbrooke's Hospital, Hill's 
      Road, Cambridge CB2 2QR, England, UK. agwn2@cam.ac.uk
FAU - Lapsley, M
AU  - Lapsley M
FAU - Lee, P J
AU  - Lee PJ
FAU - Pusey, C D
AU  - Pusey CD
FAU - Scheinman, S J
AU  - Scheinman SJ
FAU - Tam, F W
AU  - Tam FW
FAU - Thakker, R V
AU  - Thakker RV
FAU - Unwin, R J
AU  - Unwin RJ
FAU - Wrong, O
AU  - Wrong O
LA  - eng
GR  - DK 46838/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
SB  - IM
MH  - Animals
MH  - Endocytosis
MH  - Fanconi Syndrome/*complications/physiopathology
MH  - *Glomerular Filtration Rate
MH  - Humans
MH  - Male
MH  - Proteinuria/*physiopathology
MH  - Renal Insufficiency/*etiology
EDAT- 2001/11/13 10:00
MHDA- 2002/01/11 10:01
CRDT- 2001/11/13 10:00
PHST- 2001/11/13 10:00 [pubmed]
PHST- 2002/01/11 10:01 [medline]
PHST- 2001/11/13 10:00 [entrez]
AID - S0085-2538(15)48070-6 [pii]
AID - 10.1046/j.1523-1755.2001.00016.x [doi]
PST - ppublish
SO  - Kidney Int. 2001 Nov;60(5):1885-92. doi: 10.1046/j.1523-1755.2001.00016.x.