A. Evaluation method for kidney function

  • Kidney function is evaluated by estimated GFR (eGFR), which is calculated using an estimation formula based on serum creatinine value.

  • eGFR can be calculated for Japanese people using a Japanese eGFR formula based on serum creatinine value as determined by an enzymatic method.

  • The estimation formula for GFR is a simplified method. For more accurate kidney function evaluation, inulin clearance or creatinine clearance (Ccr) is recommended.

A-1. eGFR (estimated GFR)

  • The gold standard method for GFR determination is inulin clearance. However, the procedure is complicated, so eGFR is suitable in clinical settings.

  • For Japanese over 18 years old, eGFR is widely calculated by GFR equation based on serum creatinine, with the use of the simple MDRD formula in many cases. Although serum creatinine level generally starts to rise when GFR decreases to less than 50%, by using the GFR equation, mild kidney dysfunction can be detected at an earlier stage. Therefore, the GFR equation accurately estimates kidney function only in patients with GFR less than 60 mL/min/1.73 m2.

    Based on serum creatinine value level as determined by the enzymatic method, the simple Japanese formula shown below, which is a modification of the MDRD formula, is applied (Fig. 9-1):

    Fig. 9-1
    figure 1

    Nomogram for GFR estimation. A straight line is drawn between the points of age and of serum creatinine value. The eGFR value for a male or female is displayed at the point where the line crosses the axes

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    eGFR (mL/min/1.73 m 2 ) = 194 × Cr −1.094 × Age −0.287 (×0.739 if women)

    This formula is applicable only to Japanese over 18 years of age.

  • The estimation formula for GFR is a simplified method. Only 75% of cases can be estimated in the range of GFR ± 30%. In cases requiring more accurate kidney evaluation, inulin clearance or creatinine clearance (Ccr) is recommended. This accuracy is almost the same in subjects with obesity or diabetes cases. eGFR may be underestimated when agents suppressing renal tubular secretion of creatinine such as cimetidine are administered. It may be overestimated in cases with reduced muscle mass such as limb loss or muscle disease. The estimation formula is suitable for CKD patients, but its application to healthy people is not yet established.

  • The estimation formula calculates a GFR that is corrected for the standard body type (body surface area (BSA) 1.73 m2, e.g. 170 cm, 63 kg). If eGFR needs to be personalized, as for dose adjustment of a drug, it is necessary to correct it for BSA:

GFR not corrected for BSA = eGFR × BSA/1.73

A-2. Other methods

  • Kidney function can may be estimated using 24-h endogenous creatinine clearance (Ccr) in daily clinical practice.

Ccr (mL/min) = Ucr (mg/dL) × V (mL/day)/{Scr (mg/dL) × 1,440 (min/day)}

The DuBois formula, where correction for BSA calculation is made by multiplying by 1.73/BSA m2, is shown below:

BSA = (body weight kg) 0.425  × (height cm) 0.725  × 71184 × 10 −6

  • Incomplete urine collection results in an error, which is a weak point of 24-h timed creatinine clearance method. Accuracy in urine collection is assessed by the amount of creatinine excreted in urine for a day. The amount of excreted creatinine per day is constant. Since creatinine is secreted by renal tubules, creatinine clearance is higher than real GFR.

B. Evaluation of urinary findings

  • Proteinuria is important among urine abnormalities in CKD.

  • Concomitant proteinuria and hematuria is carefully managed.

  • Examination of microalbuminuria is recommended for diabetics and/or hypertensives without proteinuria.

Evaluation methods for proteinuria and proteinuria/hematuria (Fig. 9-2)

  • In a case positive for proteinuria, urinary protein is quantitatively determined for early morning spot or collected urine specimens. If urine collection is impossible, protein to creatinine ratio (UP/Ucr) is calculated.

  • When positive for both proteinuria and hematuria, detailed examination including renal biopsy is recommended.

  • In a case with isolated proteinuria, detailed examination including renal biopsy or similar examination is recommended if urinary protein is 0.5 g/day or over, or UP/Ucr is 0.5 or over.

  • Proteinuric cases of middle-aged or elderly patients often have diabetic nephropathy or nephrosclerosis. On the other hand, chronic glomerulonephritis with relatively good prognosis such as membranous nephropathy may occur with isolated proteinuria.

Fig. 9-2
figure 2

Flowchart for further examination in cases of concomitant proteinuria and hematuria

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Evaluation of isolated hematuria (Fig. 9-3)

  • When hematuria is pointed out for the first time, a further examination including diagnostic imaging is performed in search of urinary tract abnormality. If there is no urinary tract disorder, annual follow-up study is recommended.

  • If urinary symptoms or gross hematuria emerges in the course, medical consultation is strongly recommended. It is noteworthy that asymptomatic hematuria seen in an individual 40 years of age or older is associated with an increased possibility of urinary tract malignancy.

  • It is known that approximately 10% of individuals with isolated hematuria develop proteinuria in their course.

    After hematuria is complicated by proteinuria, a further examination is carried out following a flowchart in case of concomitant proteinuria and hematuria.

Fig. 9-3
figure 3

Flowchart for further examination in cases of hematuria without proteinuria

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