Optimal evaluation of results
If, for an adult, the GFR estimated by the cystatin C-based equation agrees with that estimated by the creatinine-based equation, no invasive determination of GFR is required and the GFR-estimate representing the mean of the two estimates, (eGFRcystatin C + eGFRcreatinine)/2, should be used. The closer the agreement between eGFRcystatin C and eGFRcreatinine, the more reliable is the mean value as a GFR estimate and if the eGFRcystatin C/eGFRcreatinine>-ratio is between 0.8 and 1.20 the mean value is generally reliable.
If the GFR estimates obtained by the cystatin C- and creatinine-based equations do not agree, e.g., if the eGFRcystatin C/eGFRcreatinine-ratio is outside the interval 0.8 - 1.20, a clinical evaluation of the patient has to be performed.
If the muscle mass of the patient deviates considerably from that of his/her age and sex category (e.g., because of paralysis, immobility, anorexia or excessive bodybuilding) or if the patient recently ingested boiled meat or a medicine affecting the tubular excretion of creatinine, a GFR-estimate based solely upon cystatin C should be used14-18.
If the patient is treated with large amounts of glucocorticoids his/her synthesis of cystatin C is significantly increased and in this case a GFR-estimate based solely upon creatinine (+age and sex) should be used19.
For adult patients who do not belong to any of the above-mentioned categories, an invasive determination of GFR might be required. In hyperthyroidism the cystatin C level will increase and the creatinine level decrease without corresponding changes in GFR20.
The tools of this site for estimation of GFR are based upon the cystatin C-based equation of reference 6 (the CAPA-equation) and the creatinine-based equation of references 7 and 8 (the LM-Rev-equation).
Diagnosing shrunken pore syndrome
If eGFRcystatin C is less than 70% of eGFRcreatinine, i.e. the eGFRcystatin C/eGFRcreatinine-ratio is < 0.70, and no non-renal factors influence the estimates, the patient suffers from shrunken pore syndrome with strong increase in morbidity and mortality, inter alia due to cardiovascular manifestations9-13. The increase in morbidity and mortality is inversly proportional to the eGFRcystatin C/eGFRcreatinine-ratio starting at a ratio of 0.8021. It should be emphasized that it has not yet been established that the shrunken pore syndrome exists in children younger than 18 years.
Calculating absolute GFR from relative GFR
To study the kidney function of a person, the "relative glomerular filtration rate" (relative GFR), which has the unit "mL·min-1·(1.73m2)-1", sometimes written as "mL/min/1.73 sqm", is often used.
The relative GFR of a person is thus normalized to a certain body surface area, which allows the use of virtually the same reference values for males and females, adults and children. The relative GFR of a person is accordingly also independent of his/her actual body surface area. The relative GFR is suitable for assessing and monitoring the kidney function of a patient. But if you want to correctly dose a medicine or a contrast agent mainly excreted via the kidneys, knowledge of the absolute GFR (mL/min) of the patient is required. The estimating equations accounted for above provide estimates of the relative GFR (tab ”Relative GFR”). The tab ”Absolute GFR” can be used to easily calculate the absolute GFR (mL/min) of a person from his relative GFR (mL · min-1·(1.73 m2)-1), weight and height. The DuBois and DuBois formula is thereby used to estimate body surface area22.
- Soveri I, Berg U, Björk J, Elinder CG, Grubb A, Mejare I, Sterner G, Bäck SE on behalf of the SBU review group. Measuring GFR: A Systematic Review. Am J Kidney Dis 2014; 64: 411-424.
- SBU. Methods to estimate and measure renal function (glomerular filtration rate). A systematic review. Stockholm: Swedish Council on Health Technology Assessment (SBU); 2012. SBU report no 214.
- Grubb A. Non-invasive estimation of glomerular filtration rate (GFR). The Lund model: Simultaneous use of cystatin C- and creatinine-based GFR-prediction equations, clinical data and an internal quality check. Scand J Clin Lab Invest, 2010; 70: 65 - 70
- Nyman U, Grubb A, Sterner G, Björk J: Different equations to combine creatinine and cystatin C to predict GFR. Arithmetic mean of existing equations performs as well as complex combinations. Scand J Clin Lab Invest 2009; 69: 619-627.
- Grubb A, Nyman U, Björk, J: Improved estimation of glomerular filtration rate (GFR) by comparison of eGFRcystatin C and eGFRcreatinine. Scand J Clin Lab Invest 2012; 72: 73-77.
- Grubb A, Horio M, Hansson LO, Björk J, Nyman U, Flodin M, Larssson A, Bökenkamp A, Yasuda Y, Blufpand H, Lindström V, Zegers I, Althaus H, Blirup-Jensen S, Itoh Y, Sjöström P, Nordin G, Christensson A, Klima H, Sunde K, Hjort-Christensen P, Armbruster D, Ferrero C: Generation of a new cystatin C-based estimating equation for glomerular filtration rate using seven assays standardized to the international calibrator. Clin Chem 2014; 60: 974-986. + unpublished observations
- Björk J, Grubb A, Sterner G, Nyman U: Revised equations for estimating glomerular filtration rate based on the Lund-Malmö study cohort. Scand J Clin Lab Invest 2011; 71: 232-239.
- Nyman U, Grubb A, Larsson A, Hansson L-O, Flodin M, Nordin G, Lindström V, Björk J: The revised Lund-Malmö GFR estimating equation outperforms MDRD and CKD-EPI across GFR, age and BMI intervals in a large Swedish population. Clin Chem Lab Med 2014; 52: 815-824.
- Grubb A. Cystatin C is indispensable for evaluation of kidney disease. eJIFCC 2017; 28: 269-276.
- Grubb A, Lindström V, Jonsson M, Bäck SE, Åhlund T, Rippe B, Christensson A. Reduction in glomerular pore size is not restricted to pregnant women. Evidence for a new syndrome: “Shrunken pore syndrome”. Scand J Clin Lab Invest 2015; 75: 333-340.
- Dardashti A, Nozohoor S, Grubb A, Bjursten H. Shrunken Pore Syndrome is associated with a sharp rise in mortality in patients undergoing elective coronary artery bypass grafting. Scand J Clin Lab Invest 2016; 76:74-81.
- Purde MT, Nock S, Risch L, Medina Escobar P, Greb- hardt C, Nydegger UE, Stanga Z, Risch M. The cystatin C/ creatinine ratio, a marker of glomerular filtration quality: associated factors, reference intervals, and prediction of morbidity and mortality in healthy seniors. Transl Res 2016; 169: 80–90.
- Sällman-Almén M, Björk J, Nyman U, Lindström V, Jonsson M, Abrahamson M, Schiller Vestergren AL, Lindhe Ö, Franklin G, Christensson A, Grubb A. Shrunken pore syndrome is associated with increased levels of atherosclerosis-promoting proteins. Kidney Int Rep 2019; 4: 67-79.
- Thomassen SA, Johannesen IL, Erlandsen EJ, Abrahamsen J, Randers E. Serum cystatin C as a marker of the renal function in patients with spinal cord injury. Spinal Cord 2002; 40:524-8.
- Viollet L, Gailey S, Thornton DJ, Friedman NR, Flanigan KM, Mahan JD, Mendell JR. Utility of cystatin C to monitor renal function in Duchenne muscular dystrophy. Muscle Nerve 2009;40:438–42.
- Preiss DJ, Godber IM, Lamb EJ, Dalton RN, Gunn IR. The influence of a cooked-meat meal on estimated glomerular filtration rate. Ann Clin Biochem 2007;44:35– 42.
- Tangri N, Stevens LA, Schmid CH, Zhang YL, Beck GJ, Greene T, Coresh J, Levey AS. Changes in dietary protein intake has no effect on serum cystatin C levels independent of the glomerular filtration rate. Kidney Int 2011;79:471–7.
- Blackwood WS, Maudgal DP, Pickard RG, Lawrence D, Northfield TC. Cimetidine in duodenal ulcer. Controlled trial. Lancet 1976;2:174–6.
- Risch L, Herklotz R, Blumberg A, Huber AR. Effects of glucocorticoid immunosuppression on serum cystatin C concentrations in renal transplant patients. Clin Chem 2001; 47:2055-2059.
- Karawajczyk M, Ramklint M, Larsson A. Reduced cystatin C-estimated GFR and increased creatinine-estimated GFR in comparison with iohexol-estimated GFR in a hyperthyroid patient: A case report. J Med Case Reports 2008; 2:66.
- Herou E, Dardashti A, Nozohoor S, Zindovic I, Ederoth P, Grubb A, Bjursten H. The mortality increase in cardiac surgery patients associated with shrunken pore syndrome correlates with the eGFRcystatin C/eGFRcreatinine-Ratio. Scand J Clin Lab Invest 2019; Epub ahead of print.
- DuBois D, DuBois EF. A formula to estimate the approximate surface area if height and weight be known. Arch Intern Medicine. 1916; 17:863-871.
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