Visual Abstract

Background/Aims: Autosomal dominant polycystic kidney disease (ADPKD) is a tubulointerstitial disease. Different degrees of glomerular affection in ADPKD may affect the further course of disease in which it may hypothetically be secondary to the result of glomerular involvement causing podocyte injury. Our aim was to compare urinary excretion of podocin and podocalyxin, which are biomarkers of podocyte injury, and to assess their relationship with proteinuria and renal function in ADPKD. Methods: Fifty-six patients with ADPKD and 28 volunteers were enrolled to study. Podocin, podocalyxin protein levels, and proteinuria were measured in urine. Patients were categorized based on their estimated glomerular filtration rate (eGFR). Results: Patients with ADPKD had higher podocin and podocalyxin levels compared to the control group. The levels of podocin and podocalyxin were higher in ADPKD patients both with eGFR ≥60 mL/min/1.73 m2 and with eGFR <60 mL/min/1.73 m2 than in controls. The levels of podocin and podocalyxin were higher in ADPKD patients with eGFR <60 mL/min/1.73 m2 than in ADPKD patients with eGFR ≥60 mL/min/1.73 m2. Podocin and podocalyxin were negatively correlated with eGFR and positively correlated with urine protein to creatinine ratio in ADPKD patients. Conclusion: Urine biomarkers of podocytes injury were significantly higher in ADPKD patients even in the early stage of the disease than in the control group. It should be clarified whether these biomarkers can provide new prognostic parameters for disease surveillance.

Klahr S, Breyer JA, Beck GJ, Dennis VW, Hartman JA, Roth D, et al.; Modification of Diet in Renal Disease Study Group. Dietary protein restriction, blood pressure control, and the progression of polycystic kidney disease.
J Am Soc Nephrol
. 1995 Jun;5(12):2037–47.
Fick-Brosnahan GM, Belz MM, McFann KK, Johnson AM, Schrier RW. Relationship between renal volume growth and renal function in autosomal dominant polycystic kidney disease: a longitudinal study.
Am J Kidney Dis
. 2002 Jun;39(6):1127–34.
Schrier RW, Brosnahan G, Cadnapaphornchai MA, Chonchol M, Friend K, Gitomer B, et al. Predictors of autosomal dominant polycystic kidney disease progression.
J Am Soc Nephrol
. 2014 Nov;25(11):2399–418.
Economou CG, Kitsiou PV, Tzinia AK, Panagopoulou E, Marinos E, Kershaw DB, et al. Enhanced podocalyxin expression alters the structure of podocyte basal surface.
J Cell Sci
. 2004 Jul;117(Pt 15):3281–94.
Schnabel E, Dekan G, Miettinen A, Farquhar MG. Biogenesis of podocalyxin—the major glomerular sialoglycoprotein–in the newborn rat kidney.
Eur J Cell Biol
. 1989 Apr;48(2):313–26.
Camici M. Urinary detection of podocyte injury.
Biomed Pharmacother
. 2007 Jun;61(5):245–9.
Faul C, Asanuma K, Yanagida-Asanuma E, Kim K, Mundel P. Actin up: regulation of podocyte structure and function by components of the actin cytoskeleton.
Trends Cell Biol
. 2007 Sep;17(9):428–37.
Welsh GI, Saleem MA. The podocyte cytoskeleton–key to a functioning glomerulus in health and disease.
Nat Rev Nephrol
. 2011 Oct;8(1):14–21.
Greka A, Mundel P. Cell biology and pathology of podocytes.
Annu Rev Physiol
. 2012;74(1):299–323.
Wickman L, Afshinnia F, Wang SQ, Yang Y, Wang F, Chowdhury M, et al. Urine podocyte mRNAs, proteinuria, and progression in human glomerular diseases.
J Am Soc Nephrol
. 2013 Dec;24(12):2081–95.
Chapman AB, Johnson AM, Gabow PA, Schrier RW. Overt proteinuria and microalbuminuria in autosomal dominant polycystic kidney disease.
J Am Soc Nephrol
. 1994 Dec;5(6):1349–54.
Wharram B, Goyal M, Wiggins J, Sanden SK, Hussain S, Filipiak WE, et al. Podocyte depletion causes glomerulosclerosis: diphtheria toxin-induced podocyte depletion in rats expressing human diphtheria toxin receptor transgene.
J Am Soc Nephrol
. 2005 Oct;16(10):2941–52.
Hara M, Yanagihara T, Kihara I. Urinary podocytes in primary focal segmental glomerulosclerosis.
. 2001 Nov;89(3):342–7.
Bhathena DB. Glomerular basement membrane length to podocyte ratio in human nephronopenia: implications for focal segmental glomerulosclerosis.
Am J Kidney Dis
. 2003 Jun;41(6):1179–88.
Pollak MR. The genetic basis of FSGS and steroid-resistant nephrosis.
Semin Nephrol
. 2003 Mar;23(2):141–6.
Wu DT, Bitzer M, Ju W, Mundel P, Böttinger EP. TGF-beta concentration specifies differential signaling profiles of growth arrest/differentiation and apoptosis in podocytes.
J Am Soc Nephrol
. 2005 Nov;16(11):3211–21.
Gohh RY, Yango AF, Morrissey PE, Monaco AP, Gautam A, Sharma M, et al. Preemptive plasmapheresis and recurrence of FSGS in high-risk renal transplant recipients.
Am J Transplant
. 2005 Dec;5(12):2907–12.
Fischer EG, Moore MJ, Lager DJ. Fabry disease: a morphologic study of 11 cases.
Mod Pathol
. 2006 Oct;19(10):1295–301.
Nasr SH, Preddie DC, Markowitz GS, Appel GB, D’Agati VD. Multiple myeloma, nephrotic syndrome and crystalloid inclusions in podocytes.
Kidney Int
. 2006 Feb;69(3):616–20.
Tanner GA, Evan AP, Summerlin PB, Knopp LC. Glomerular and proximal tubular morphology after single nephron obstruction.
Kidney Int
. 1989 Dec;36(6):1050–60.
Gandhi M, Olson JL, Meyer TW. Contribution of tubular injury to loss of remnant kidney function.
Kidney Int
. 1998 Oct;54(4):1157–65.
Price JD, Palmer RA. A functional and morphological follow-up study of acute renal failure.
Arch Intern Med
. 1960 Jan;105(1):90–8.
Ravine D, Gibson RN, Walker RG, Sheffield LJ, Kincaid-Smith P, Danks DM. Evaluation of ultrasonographic diagnostic criteria for autosomal dominant polycystic kidney disease 1.
. 1994 Apr;343(8901):824–7.
Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D; Modification of Diet in Renal Disease Study Group. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation.
Ann Intern Med
. 1999 Mar;130(6):461–70.
Hara M, Yamamoto T, Yanagihara T, Takada T, Itoh M, Adachi Y, et al. Urinary excretion of podocalyxin indicates glomerular epithelial cell injuries in glomerulonephritis.
. 1995;69(4):397–403.
Hara M, Yanagihara T, Itoh M, Matsuno M, Kihara I. Immunohistochemical and urinary markers of podocyte injury.
Pediatr Nephrol
. 1998 Jan;12(1):43–8.
Nakamura T, Ushiyama C, Suzuki S, Hara M, Shimada N, Ebihara I, et al. Urinary excretion of podocytes in patients with diabetic nephropathy.
Nephrol Dial Transplant
. 2000 Sep;15(9):1379–83.
Chapman AB, Johnson A, Gabow PA, Schrier RW. The renin-angiotensin-aldosterone system and autosomal dominant polycystic kidney disease.
N Engl J Med
. 1990 Oct;323(16):1091–6.
Meijer E, Rook M, Tent H, Navis G, van der Jagt EJ, de Jong PE, et al. Early renal abnormalities in autosomal dominant polycystic kidney disease.
Clin J Am Soc Nephrol
. 2010 Jun;5(6):1091–8.
Hodgkins KS, Schnaper HW. Tubulointerstitial injury and the progression of chronic kidney disease.
Pediatr Nephrol
. 2012 Jun;27(6):901–9.
Kerjaschki D, Sharkey DJ, Farquhar MG. Identification and characterization of podocalyxin–the major sialoprotein of the renal glomerular epithelial cell.
J Cell Biol
. 1984 Apr;98(4):1591–6.
Torres VE, Harris PC. Autosomal dominant polycystic kidney disease: the last 3 years.
Kidney Int
. 2009 Jul;76(2):149–68.
Ecder T, Schrier RW. Hypertension in autosomal-dominant polycystic kidney disease: early occurrence and unique aspects.
J Am Soc Nephrol
. 2001 Jan;12(1):194–200.
Kazancioglu R, Ecder T, Altintepe L, Altiparmak MR, Tuglular S, Uyanik A, et al.; Turkish Society of Nephrology Polycystic Kidney Disease Working Group. Demographic and clinical characteristics of patients with autosomal dominant polycystic kidney disease: a multicenter experience.
Nephron Clin Pract
. 2011;117(3):c270–5.
Wang G, Lai FM, Kwan BC, Lai KB, Chow KM, Li PK, et al. Podocyte loss in human hypertensive nephrosclerosis.
Am J Hypertens
. 2009 Mar;22(3):300–6.
Nagase M, Shibata S, Yoshida S, Nagase T, Gotoda T, Fujita T. Podocyte injury underlies the glomerulopathy of Dahl salt-hypertensive rats and is reversed by aldosterone blocker.
. 2006 Jun;47(6):1084–93.
Kretzler M, Koeppen-Hagemann I, Kriz W. Podocyte damage is a critical step in the development of glomerulosclerosis in the uninephrectomised-desoxycorticosterone hypertensive rat.
Virchows Arch
. 1994;425(2):181–93.
Wang Y, Zhao S, Loyd S, Groome LJ. Increased urinary excretion of nephrin, podocalyxin, and βig-h3 in women with preeclampsia.
Am J Physiol Renal Physiol
. 2012 May;302(9):F1084–9.
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