Screening for chronic kidney disease of uncertain aetiology in Sri Lanka: usability of surrogate biomarkers over dipstick proteinuriaReport as inadecuate

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BMC Nephrology

, 18:199

Epidemiology and Health Outcomes


BackgroundThe use of dipstick proteinuria to screen Chronic Kidney Disease of uncertain aetiology CKDu in Sri Lanka is a recently debated matter of dispute. The aim of this study was to assess the suitability of biomarkers: serum creatinine, cystatin C and urine albumin to creatinine ratio ACR for screening CKDu in Sri Lanka.

MethodsForty-four male CKDu patients and 49 healthy males from a CKDu-endemic region were selected. Meanwhile, 25 healthy males from a non-endemic region were selected as an absolute control. The diagnostic accuracy of each marker was compared using the above three study groups.

ResultsIn receiver operating characteristics ROC plots for creatinine, cystatin C and ACR, values of area under the curve AUC were 0.926, 0.920 and 0.737 respectively when CKDu was compared to non-endemic control. When CKDu was compared to endemic control, AUCs of above three analytes were distinctly lower as 0.718, 0.808 and 0.678 respectively. Cystatin C exhibited the highest sensitivity for CKDu when analyzed against both control groups where respective sensitivities were 0.75 against endemic control and 0.89 against non-endemic control. ROC-optimal cutoff limits of creatinine, cystatin C and ACR in CKDu vs non-endemic control were 89.0 μmol-L, 1.01 mg-L and 6.06 mg-g-Cr respectively, whereas in CKDu vs endemic control the respective values were 111.5 μmol-L, 1.22 mg-L and 12.66 mg-g-Cr.

ConclusionsAmongst the three biomarkers evaluated in this study, our data suggest that Cystatin C is the most accurate functional marker in detecting CKDu in endemic regions, yet the high cost hinders its usability on general population. Creatinine is favorable over dipstick proteinuria owing to its apparent accuracy and cost efficiency, while having the ability to complement the kidney damage marker ACR in screening. ACR may not be favorable as a standalone screening marker in place of dipstick proteinuria due to its significant decline in sensitivity against the CKDu-endemic population. However, creatinine and ACR in a complementary manner could overcome current shortcomings of dipstick proteinuria and such a dual marker tool could be commodious in screening CKDu-type tubulointerstital diseases. Furthermore, use of ACR may also increase the ability to clinically discriminate CKDu from other glomerular nephropathies.

KeywordsCKDu Proteinuria Biomarkers AbbreviationsACRAlbumin to creatinine ratio

AUCArea under curve

CIConfidence Interval

CKDuChronic kidney disease of uncertain aetiology

eGFRestimated Glomerular Filtration Rate

ESRDEnd Stage Renal Disease

MDRDModification of Diet for Renal Disease

NCPNorth Central Province

RAASRenin Angiotensin- Aldosterone System

ROCReceiver operating characteristic

S.CrSerum creatinine

S.CysSerum cystatin C

SDStandard deviation



Author: Samantha Ratnayake - Zeid Badurdeen - Nishantha Nanayakkara - Tilak Abeysekara - Neelakanthi Ratnatunga - Ranjith Kumarasiri


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