Masahiro Matsuki*,Toshiaki TanakaTakeshi Maehana Koji IchiharaMasahiro Yanase,Masanori Matsukawa, Hideki Adachi,Satoshi TakahashiNaoya Masumori

aDepartment of Urology,Sapporo Medical University,School of Medicine,Sapporo,Japan

bSapporo Kidney Disease Treatment Forum,Sapporo,Japan

cDepartment of Urology,Sunagawa City Medical Center,Sunagawa,Japan

dDepartment of Urology,Takikawa Municipal Hospital,Takikawa,Japan

eDepartment of Urology,SaiseikaiOtaru Hospital,Otaru,Japan

CLINICAL EXPERIENCE

Serum cystatin C can be used as a marker of renal function even in patients with intestinal urinary diversion

Masahiro Matsukia,b,*,Toshiaki Tanakaa,b,Takeshi Maehanaa,b, Koji Ichiharaa,b,Masahiro Yanaseb,c,Masanori Matsukawab,d, Hideki Adachib,e,Satoshi Takahashia,b,Naoya Masumoria,b

aDepartment of Urology,Sapporo Medical University,School of Medicine,Sapporo,Japan

bSapporo Kidney Disease Treatment Forum,Sapporo,Japan

cDepartment of Urology,Sunagawa City Medical Center,Sunagawa,Japan

dDepartment of Urology,Takikawa Municipal Hospital,Takikawa,Japan

eDepartment of Urology,SaiseikaiOtaru Hospital,Otaru,Japan

Objective:Recently,serum cystatin C(CysC)has been used as a novel marker of renal function.However,there is a lack of data on CysC levels in patients with intestinal urinary diversion(UD).Here we report CysC levels in such patients.

Renal function;

Cystatin C;

Urinary diversion

Conclusion:The correlation between CysC and sCr was strong and the correlation coeff i cient was equivalent to that in patients without UD.The results suggest that CysC is not affected by UD and can be used as a marker of renal function similarly to sCr in patients with UD.

a2015 Editorial Off i ce of Asian Journal of Urology.Production and hosting by Elsevier (Singapore)Pte Ltd.This is an open access article under the CC BY-NC-ND license(http:// creativecommons.org/licenses/by-nc-nd/4.0/). Radical cystectomy and intestinal urinary diversion(UD) such as ileal conduit and ilealneobladder substitution are standard treatments for patients with localized muscle invasive bladder cancer.Some patients can obtain longterm survival postoperatively but deterioration of the renal function should be considered as an important complication in the late period[1].

Although inulin clearance is the gold standard for evaluation of renal function,the procedure is too complicated for routine use in the clinical setting.Therefore,renal function is generally evaluated by serum creatinine(sCr) and the estimated glomerular f i ltration rate(eGFR)based on sCr.Recently,serum cystatin C(CysC)has been used as a novel marker of renal function[2].CysC is not affected by the amount of muscle or the diet,unlike sCr.In addition, the calculation of eGFR using CysC provides better accuracy than eGFR based on sCr alone[3].

In patients with UD,substances in the urine can be absorbed by the ileal mucosa exposed to the urine[4], which may affect their concentrations in the serum.To date,there has been a lack of data on CysC levels in patients with UD.Here we report CysC levels in such patients.

This study was a prospective observational study of patients who were diagnosed with bladder cancer and subsequently treated with radical cystectomy and UD at Sapporo Medical University Hospital and its aff i liated hospitals between 2012 and 2013.The protocol was approved by the institutional review board(acceptance number 23e132).sCr and CysC were obtained optionally at the same time at least 1 month after radical cystectomy and UD.eGFR based on sCr(eGFRcreat)was calculated as follows:eGFRcreat(mL/min/1.73 m2)Z 194?Cr?1.094?age?0.287(in females:?0.739)[5].eGFR based on CysC (eGFRcys)was calculated as follows:eGFRcys(mL/min/ 1.73 m2)Z(104?CysC?1.019?0.996age)?8(in females: (104?CysC?1.019?0.996age?0.929)?8)[6].Spearman’s rank correlation analysis was performed between sCr, sCysC,and eGFRcreat as well as eGFRcys and eGFRcreat.

Totally,38 patients consisting of 33 males and f i ve females were enrolled in this study.Their median age was 71 years(range 50e84 years).Of them,33(86.8%)and f i ve (13.2%)had an ileal conduit and ilealneobladder,respectively.The median CysC and median sCr concentrations were 1.12 mg/L(range 0.75e2.47 mg/L)and 0.99 mg/dL (range 0.61e2.22 mg/dL),respectively.The median eGFR-cys and eGFRcreat levels were 61.08 mL/min/1.73 m2(range 22.64e99.89 mL/min/1.73 m2)and 58.01 mL/min/ 1.73 m2(range 23.48e91.82 mL/min/1.73 m2),respectively.CysChadasignif i cantcorrelationwith sCr(r Z 0.8607,p<0.0001)and eGFRcreat(r Z?0.8993, p<0.0001)(Fig.1).eGFRcys also had a signif i cant correlation with eGFRcreat(r Z 0.8104,p<0.0001)(Fig.2).

To the best of our knowledge,this is the f i rst report measuring CysC in patients with UD.The correlation between CysC and sCr was strong and the correlation coeff icient was equivalent to that in patients without UD[7].The results of this study suggest that CysC can be used as a marker of renal function similarly to sCr and eGFRcreat in patients with UD.

In patients with UD,substances in the urine can be reabsorbed by the ileal mucosa exposed to the urine. Rinnab et al.[4]reported that urinary creatinine and urea were potentially reabsorbed into the ilealneobladder, which could affect their concentrations in the serum, although the status was different among individuals and the clinical signi fi cance was not determined.Cystatin C in the urine can also potentially be absorbed in the ileal segment. However,the urinary concentration of cystatin C in normal subjects is low[8]because cystatin C is absorbed and rapidly degraded by the proximal tubular cells after being fi ltered in the glomeruli[9].Therefore,the serum concentration may barely be affected even if urinary cystatin C is absorbed by the ileal mucosa.Essentially,the relationship between CysC and inulin clearance should be veri fi ed. However,sCr has been used to assess renal function in patients with UD[1]and the compatibility between CysC and sCr may indicate the clinical usefulness of CysC. Because CysC provides more accuracy in calculation of eGFR,the KDIGO 2012 clinical practice guideline[10] recommend the use of eGFR considering CysC.Therefore we should assess renal function by using CysC to manage chronic kidney disease in patients with UD.

Conf l icts of interest

The authors declare no conf l ict of interest.

Acknowledgments

This study was performed with the cooperation of the Departments of Urology of the following hospitals:Hakodate Goryokaku Hospital(Hakodate,Japan),Oji General Hospital(Tomakomai,Japan),Hokkaido Social Work Association Obihiro Hospital(Obihiro,Japan),Steel Memorial Muroran Hospital(Muroran,Japan),and NTT-East Corporation Sapporo Medical Center(Sapporo,Japan).

[1]Eisenberg MS,Thompson RH,Frank I,Kim SP,Cotter KJ, Tollefson MK,et al.Long-term renal function outcomes after radical cystectomy.J Urol 2014;191:619e25.

[2]Onopiuk A,Tokarzewicz A,Gorodkiewicz E.Cystatin C: a kidney function biomarker.Adv Clin Chem 2015;68: 57e69.

[3]Stevens LA,Coresh J,Schmid CH,Feldman HI,Froissart M, Kusek J,et al.Estimating GFR using serum cystatin C alone and in combination with serum creatinine:a pooled analysis of 3,418 individuals with CKD.Am J Kidney Dis 2008;51:395e406.

[4]Rinnab L,Straub M,Hautmann RE,Braendle E.Postoperative resorptive and excretory capacity of the ileal neobladder.BJU Int 2005;95:1289e92.

[5]Matsuo S,Imai E,Horio M,Yasuda Y,Tomita K,Nitta K,et al. Revised equations for estimated GFR from serum creatinine in Japan.Am J Kidney Dis 2009;53:982e92.

[6]Horio M,Imai E,Yasuda Y,Watanabe T,Matsuo S.GFR estimation using standardized serum cystatin C in Japan.Am J Kidney Dis 2013;61:197e203.

[7]Okuda Y,Namba S,Nagata M,Hara H,Morita T.Plasma creatinine and cystatin C ratio is useful for discriminate diagnosis of postrenal renal failure.Rinsho Byori 2008;56: 101e7.

[8]Uchida K,Gotoh A.Measurement of cystatin-C and creatinine in urine.Clin Chim Acta 2002;323:121e8.

[9]Tenstad O,Roald AB,Grubb A,Aukland K.Renal handling of radiolabelled human cystatin C in the rat.Scand J Clin Lab Invest 1996;56:409e14.

[10]KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease.Kidney Int Suppl 2013; 3:19e62.

Received 12 April 2015;received in revised form 23 June 2015;accepted 8 July 2015 Available online 15 July 2015

*Corresponding author.Department of Urology,Sapporo Medical University,School of Medicine,Sapporo,Japan.

E-mail address:mtkmatsuki@yahoo.co.jp(M.Matsuki).

Peer review under responsibility of Shanghai Medical Association and SMMU.

http://dx.doi.org/10.1016/j.ajur.2015.07.003

2214-3882/a2015 Editorial Off i ce of Asian Journal of Urology.Production and hosting by Elsevier(Singapore)Pte Ltd.This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).

Methods:We prospectively observed 38 patients who were diagnosed with bladder cancer and subsequently treated with radical cystectomy and UD at our institution in 2012 and 2013. Serum creatinine(sCr)and CysC were obtained optionally at the same time at least 1 month after radical cystectomy and UD.

Results:The median CysC and sCr concentrations were 1.12 mg/L(range 0.75e2.47 mg/L)and 0.99 mg/dL(range 0.61e2.22 mg/dL),respectively.The median estimated concentrations of glomerular f i ltration rate(GFR)based on CysC(eGFRcys)and GFR based on creatinine(eGFR-creat)were 61.08 mL/min/1.73 m2(range 22.64e99.89 mL/min/1.73 m2)and 58.01 mL/min/ 1.73 m2(range 23.48e91.82 mL/min/1.73 m2),respectively.CysC had a signif i cant correlation with sCr(r Z 0.8607,p<0.0001)and eGFRcreat(r Z?0.8993,p<0.0001).eGFRcys also had a signif i cant correlation with eGFRcreat(r Z 0.8104,p<0.0001).