Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Pediatric Nephrology
Published in: Pediatric Nephrology 10/2013

01-10-2013 | Original Article

The role of urinary TGF-β1, TNF-α, IL-6 and microalbuminuria for monitoring therapy in posterior urethral valves

Authors: Ankur Mandelia, Minu Bajpai, Sandeep Agarwala, Arun K. Gupta, Rakesh Kumar, Abid Ali

Published in: Pediatric Nephrology | Issue 10/2013

Login to get access

Abstract

Background

Long-term renal deterioration is common in patients with posterior urethral valves (PUV), and early identification of detrimental factors can help in counselling patients as well as in guiding future therapy. The aim of our study was (1) to evaluate urinary transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) levels and microalbuminuria before and after ablation of PUV and (2) to examine the effect of early induction of angiotensin-converting enzyme inhibitors (ACE-I) on renal recovery.

Methods

The study included 30 patients with diagnosed PUV. Urinary cytokines were measured pre-operatively and post-operatively for 1 year. The study group was subdivided into two subgroups at 6 months after surgery. Group 1 included 16 patients whose urinary TGF-β1 level showed a declining trend. Group 2 included 14 patients whose urinary TGF-β1 showed a rising trend or plateaued; these patients were started on ACE-I therapy, which they received for at least 6 months.

Results

Urinary TGF-β1, TNF-α and microalbumin levels were high in patients with PUV. In Group 1 patients, urinary TGF-β1, TNF-α and microalbumin levels fell significantly following valve ablation and continued to decline for 12 months. In Group 2 patients, after an initial fall following valve ablation, urinary TGF-β1, TNF-α and microalbumin showed a continued rise until 6 months post-surgery. After ACE-I therapy, there was 53.43 % fall in urinary TGF-β1, 43.15 % fall in microalbuminuria, 28.57 % improvement in split renal function and 35.80 % improvement in GFR.

Conclusions

Based on our results, urinary TGF-β1, urinary TNF-α and microalbuminuria can be used as biomarkers for the early recognition of ongoing renal damage in patients with PUV. ACE-I plays a role in retarding renal damage in these patients.
Literature
1.
Parkhouse HF, Barratt TM, Dillon MJ, Duffy PG, Fay J, Ransley PG, Woodhouse CR, Williams DI (1988) Long-term outcome of boys with posterior urethral valves. Br J Urol 62:59–62PubMedCrossRef
2.
Kohaut EC, Tejani A (1996) The 1994 annual report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Nephrol 10:422–434PubMedCrossRef
3.
Smith GHH, Canning DA, Schulmann SL, Snyder HM 3rd, Duckett JW (1996) The long-term outcome of posterior urethral valves treated with primary valve ablation and observation. J Urol 155:1730–1734PubMedCrossRef
4.
Tejani A, Butt K, Glassberg K, Price A, Gurumurthy K (1986) Predictors of eventual end stage renal disease in children with posterior urethral valves. J Urol 136:857–860PubMed
5.
Bajpai M, Dave S, Gupta DK (2001) Factors affecting outcome in the management of posterior urethral valves. Pediatr Surg Int 17:11–15PubMedCrossRef
6.
Yarger WE, Schoken DD, Harris RH (1980) Obstructive nephropathy in the rat: possible roles for renin-angiotensin system, prostaglandins, and thromboxanes in post-obstructive renal function. J Clin Invest 65:400–412PubMedCrossRef
7.
Chevalier RL, Goyal S, Kim A, Chang AY, Landau D, LeRoith D (2000) Renal tubulointerstitial injury from ureteral obstruction in the neonatal rat is attenuated by IGF-1. Kidney Int 57:882–890PubMedCrossRef
8.
Bajpai M, Pal K, Bal CS, Gupta AK, Pandey RM (2003) Role of plasma renin activity in the management of primary vesicoureteric reflux: a preliminary report. Kidney Int 64:1643–1647PubMedCrossRef
9.
Toke A, Meyer TW (2001) Hemodynamic effects of angiotensin II in the kidney. Contrib Nephrol 135:34–46PubMedCrossRef
10.
Kagami S, Border WA, Miller DE, Noble NA (1994) Angiotensin II stimulates extracellular matrix protein synthesis through induction of transforming growth factor-beta expression in rat glomerular mesangial cells. J Clin Invest 93:2431–2437PubMedCrossRef
11.
Masson P, Ohlsson P, Bjorkhem I (1981) Combined enzymic-Jaffe method for determination of creatinine in serum. Clin Chem 27:18–21PubMed
12.
Bajpai M, Pratap A, Tripathi M, Bal CS (2005) Posterior urethral valves: preliminary observations on the significance of plasma renin activity as a prognostic marker. J Urol 173:592–594PubMedCrossRef
13.
Peters H, Noble NA, Border WA (1997) Transforming growth factor-β in human glomerular injury. Curr Opin Nephrol Hypertens 6:389–393PubMedCrossRef
14.
Sharma K, Ziyadeh F, Alzahabi B, McGowan TA, Kapoor S, Kurnik BR, Kurnik PB, Weisberg LS (1997) Increased renal production of transforming growth factor-β1 in patients with type II diabetes. Diabetes 46:854–859PubMedCrossRef
15.
Murakami K, Takemura T, Hino S, Yoshioka K (1997) Urinary transforming growth factor-β1 in patients with glomerular diseases. Pediatr Nephrol 11:334–336PubMedCrossRef
16.
Kanai H, Mitsuhashi H, Ono K, Yano S, Naruse T (1994) Increased excretion of urinary transforming growth factor β in patients with focal glomerular sclerosis. Nephron 66:391–395PubMedCrossRef
17.
Shihab F, Yamamoto T, Nast C, Cohen AH, Noble NA, Gold LI, Border WA (1995) Transforming growth factor-β and matrix protein expression in acute and chronic rejection of human renal allografts. J Am Soc Nephrol 6:286–294PubMed
18.
Klahr S, Morrissey J (1998) The role of growth factors, cytokines and vasoactive compounds in obstructive nephropathy. Semin Nephrol 18:622–632PubMed
19.
Seremetis GM, Maizels M (1996) TGF-b1 mRNA expression in the renal pelvis after experimental and clinical ureteropelvic junction obstruction. J Urol 156:261–266PubMedCrossRef
20.
MacRae Dell K, Hoffman BB, Leonard MB, Ziyadeh FN, Schulman SL (2000) Increased urinary transforming growth factor-beta1 excretion in children with posterior urethral valves. Urology 56:311–314PubMedCrossRef
21.
Palmer LS, Maizels M, Kaplan WE, Firlit CF, Cheng EY (1997) Urine levels of transforming growth factor-beta 1 in children with ureteropelvic junction obstruction. Urology 50:769–773PubMedCrossRef
22.
Furness P, Maizels M, Han SW, Cohn RA, Cheng EY (1999) Elevated bladder urine concentration of transforming growth factor-β 1 correlates with upper urinary tract obstruction in children. J Urol 162:1033–1036PubMedCrossRef
23.
El-Sherbiny MT, Mousa OM, Shokeir AA, Ghoneim MA (2002) Role of urinary transforming growth factor-β1 concentration in the diagnosis of upper urinary tract obstruction in children. J Urol 168:1798–1800PubMedCrossRef
24.
Yang Y, Hou Y, Wang CL, Ji SJ (2006) Renal expression of epidermal growth factor and transforming growth factor-beta1 in children with congenital hydronephrosis. Urology 67:817–821PubMedCrossRef
25.
Taha MA, Shokeir AA, Osman HG, Abd El-Aziz A-A, Farahat SE (2007) Pelvi-ureteric junction obstruction in children: the role of urinary transforming growth factor-beta and epidermal growth factor. BJU Int 99:899–903PubMedCrossRef
26.
Ishidoya S, Morrissey J, McCracken R, Klahr S (1996) Delayed treatment with enalapril halts tubulointerstitial fibrosis in rats with obstructive nephropathy. Kidney Int 49:1110–1119PubMedCrossRef
27.
Zoja C, Donadelli R, Corna D, Testa D, Facchinetti D, Maffi R, Luzzana E, Colosio V, Bertani T, Remuzzi G (1997) The renoprotective properties of angiotensin-converting enzyme inhibitors in a chronic model of membranous nephropathy are solely due to the inhibition of angiotensin II: Evidence based on comparative studies with a receptor antagonist. Am J Kidney Dis 29:254–264PubMedCrossRef
28.
Zoja C, Abbate M, Corna D, Capitanio M, Donadelli R, Bruzzi I, Oldroyd S, Benigni A, Remuzzi G (1998) Pharmacologic control of angiotensin II ameliorates renal disease while reducing renal TGF-β in experimental mesangioproliferative glomerulonephritis. Am J Kidney Dis 31:453–463PubMedCrossRef
29.
Wolf G, Schneider A, Wenzel U, Helmchen U, Stahl RA (1998) Regulation of glomerular TGF-β expression in the contralateral kidney of two-kidney, one-clip hypertensive rats. J Am Soc Nephrol 9:763–772PubMed
30.
Obata JE, Nakamura T, Kuroyanagi R, Yoshida Y, Guo DF, Inagami T (1997) Candesartan prevents the progression of glomerulosclerosis in genetic hypertensive rats. Kidney Int 52:S229–S231CrossRef
31.
Shin GT, Kim SJ, Ma KA, Kim HS, Kim D (2000) ACE inhibitors attenuate expression of renal transforming growth factor-β in humans. Am J Kidney Dis 36:894–902PubMedCrossRef
32.
Stenvinkel P, Ketteler M, Johnson RJ, Lindholm B, Pecoits-Filho R, Riella M, Heimbürger O, Cederholm T, Girndt M (2005) IL-10, IL-6, and TNF-alpha: central factors in the altered cytokine network of uremia—the good, the bad, and the ugly. Kidney Int 67:1216–1233PubMedCrossRef
33.
Roilides E, Papachristou F, Gioulekas E, Tsaparidou S, Karatzas N, Sotiriou J, Tsiouris J (1999) Increased urine interleukin-6 concentrations correlate with pyelonephritic changes on 99 m Tc dirmecapto succinic acid scans in neonates with urinary tract infections. J Infect Dis 180:904–907PubMedCrossRef
34.
Haraoka M, Senoh K, Ogata N, Furukawa M, Matsumoto T, Kumazawa J (1996) Elevated interleukin-8 levels in the urine of children with renal scarring and/or vesicoureteral reflux. J Urol 155:678–680PubMedCrossRef
35.
Gokce I, Alpay H, Biyikli N, Unluguzel G, Dede F, Topuzoglu A (2010) Urinary levels of interleukin-6 and interleukin-8 in patients with vesicoureteral reflux and renal parenchymal scar. Pediatr Nephrol 5:905–912CrossRef
36.
Tramma D, Hatzistylianou M, Gerasimou G, Lafazanis V (2012) Interleukin-6 and interleukin-8 levels in the urine of children with renal scarring. Pediatr Nephrol 27:1525–1530PubMedCrossRef
37.
Madsen MG, Norregaard R, Stodkilde L, Christensen JH, Jørgensen TM, Frøkiær J (2012) Urine and kidney cytokine profiles in experimental unilateral acute and chronic hydronephrosis. Scand J Urol Nephrol 46:91–96PubMedCrossRef
38.
Ruiz-Deya G, Sikka SC, Thomas R, Abdel-Mageed AB (2002) Potential role for the nuclear transcription factor NF-kappa β in the pathogenesis of ureteropelvic junction obstruction. J Endourol 16:611–615PubMedCrossRef
39.
Misseri R, Meldrum DR, Dinarello CA, Dagher P, Hile KL, Rink RC, Meldrum KK (2005) TNF-α mediates obstruction-induced renal tubular cell apoptosis and proapoptotic signalling. Am J Physiol Renal Physiol 288:F406–F411PubMedCrossRef
40.
Kaneto H, Morrissey JJ, McCracken R, Ishidoya S, Reyes AA, Klahr S (1996) The expression of mRNA for tumor necrosis factor α increases in the obstructed kidney of rats soon after unilateral ureteral ligation. Nephrology 2:161–166CrossRef
41.
Valles PG, Pascual L, Manucha W, Carrizo L, Rüttler M (2003) Role of endogenous nitric oxide in unilateral ureteropelvic junction obstruction in children. Kidney Int 63:1104–1115PubMedCrossRef
42.
Chevalier RL (2006) Obstructive nephropathy: towards biomarker discovery and gene therapy. Nat Clin Pract Nephrol 2:157–168PubMedCrossRef
43.
Lopez Pereira P, Espinosa L, Martinez Urrutina MJ, Lobato R, Navarro M, Jaureguizar E (2003) Posterior urethral valves: prognostic factors. BJU Int 91:687–690PubMedCrossRef
44.
Bajpai M, Bal CS, Kumar R, Chaturvedi PK, Kalaivani M, Gupta AK (2011) Persistent renin–angiotensin system activation after anti-reflux surgery and its management. J Pediatr Urol 7:616–622PubMedCrossRef
45.
Marcussen N, Olsen TS (1990) Atubular glomeruli in patients with chronic pyelonephritis. Lab Invest 62:467–473PubMed
Metadata
Title
The role of urinary TGF-β1, TNF-α, IL-6 and microalbuminuria for monitoring therapy in posterior urethral valves
Authors
Ankur Mandelia
Minu Bajpai
Sandeep Agarwala
Arun K. Gupta
Rakesh Kumar
Abid Ali
Publication date
01-10-2013
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 10/2013
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-013-2506-8

Other articles of this Issue 10/2013

Pediatric Nephrology 10/2013 Go to the issue

Original Article

Associations between fibroblast growth factor 23 and cardiac characteristics in pediatric heart failure

Review

The evolving ethics of infant dialysis

Original Article

Growth and maturation improvement in children on renal replacement therapy over the past 20 years

Letter to the Editors

Chronic cyclosporine-induced nephrotoxicity in children with steroid-resistant nephrotic syndrome

Brief Report

Hemolytic uremic syndrome complicating Mycoplasma pneumoniae infection

Review

HDAC inhibitors in kidney development and disease