Kobayashi et al.

BMC Nephrology (2019) 20:306

https://doi.org/10.1186/s12882-019-1486-8

RESEARCH ARTICLE Open Access

Spot urine protein/creatinine ratio as a

reliable estimate of 24-hour proteinuria in
patients with immunoglobulin A
nephropathy, but not membranous
nephropathy
Seiji Kobayashi1,2*, Hoichi Amano1,3, Hiroyuki Terawaki4, Makoto Ogura1, Yoshindo Kawaguchi1 and Takashi Yokoo1

Abstract
Background: Proteinuria is known to be associated with both kidney function deterioration and cardiovascular
diseases. While proteinuria estimation from 24-h urine samples has traditionally been considered as the standard
method for assessment of the degree of urinary protein excretion, sample collection is associated with several
technical problems such as inaccurate collection and the potential spread of drug-resistant pathogens. Therefore,
the spot urine protein/creatinine ratio (PCR) assessment is currently recommended as an alternative. While the
utility of PCR has been validated, studies on the association between spot urine PCR and 24-h proteinuria (24HP) in
patients with chronic glomerular nephritis (CGN) and nephrotic syndrome (NS) are limited. This study aimed to
evaluate whether an estimated result from a spot urine PCR could sufficiently approximate the daily urine protein
excretion amount from a 24-h urine sample in patients with immunoglobulin A nephropathy (IgAN), minimal
change disease (MCD), and membranous nephropathy– nephrotic syndrome (MN-NS).
Methods: The study participants included 161 patients with IgAN, MCD, or MGN-NS at the Jikei University Kashiwa
Hospital and Kanagawa Prefecture Shiomidai Hospital. The correlation between spot urine PCR and a 24-h urine
protein was investigated using linear regression analysis with Spearman’s correlation (r) coefficient and intraclass
correlation coefficient (ICC).
Results: While high correlation coefficients (r = 0.86, P < 0.001) and substantial agreement (ICC: 0.806, P < 0.001)
were observed in patients with IgAN, similar correlations were not observed in patients with MCD or MN-NS. In the
patients with MCD, r was 0.53 (P < 0.001), which signified a slight correlation, and in the patients with MN-NS, r was
0.289 (P = 0.17), which was not statistically significant.
Conclusions: This study revealed that spot urine PCR is a reliable estimate of 24HP value in patients with IgAN. In
contrast, there is a considerable difference between the daily urine protein excretion amount based on a 24-h urine
sample and that which is calculated from spot urine PCR in patients with NS.
Keywords: 24-h urine, Urine protein excretion, Proteinuria, Nephrotic syndrome, Minimal change disease,
Immunoglobulin a nephropathy

* Correspondence: seiji-kobayashi@nms.ac.jp
1
Division of Nephrology and Hypertension, Department of Internal Medicine,
The Jikei University School of Medicine, Tokyo, Japan
2
Department of Allergy and Rheumatology, Nippon Medical School Graduate
School of Medicine, Tokyo, Japan
Full list of author information is available at the end of the article

© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Kobayashi et al. BMC Nephrology (2019) 20:306 Page 2 of 7

Background Japan) at each hospital. Estimated glomerular filtration

Accumulating evidence shows that assessment of pro- rate (eGFR) is expressed using the following formula:
teinuria plays an important role in the diagnosis of eGFR (mL/min/1.73 m2) =194 × Cr − 1.094age-0.287 (×
kidney disease and in monitoring disease activity [1–3]. 0.739, if female) prepared by the Japanese Society of
In addition, increase in proteinuria is not only a risk fac- Nephrology [3].
tor for kidney function decline but also for cardiovascu- All participants were given explanations on the use of
lar disease [4, 5]. Therefore, assessment of the actual the device for proportionally collectable urine at a rate
amount of proteinuria is crucial. of 1/50 (Urine-MatePR , Sumitomo Bekelite, Tokyo,
The standard method to assess proteinuria is the pro- Japan) for each voiding for 24 h. Casual spot urine was
tein content of an accurately collected 24-h urine sample obtained in the morning of the same day after a patient
[6]. However, some problems are encountered in collect- carried out collection of 24-h urine. Urinary concentra-
ing such samples. First, such collection is cumbersome tion of protein and Cr were measured by Japan Electron
and frequently inaccurate owing to collection error [7]. Optics Laboratory autoanalyzer, Tokyo, Japan.
Second, collection of 24-h urine in the hospital can cause
spread of some species of bacteria, such as multidrug-re- Histopathological diagnosis
sistant Pseudomonas aeruginosa, which causes urinary All kidney tissue specimens were obtained via percutan-
tract infection [8, 9]. eous needle biopsies. All specimens were examined
The Japanese Society of Nephrology or Kidney Disease using light microscopy; immunohistochemistry, includ-
Outcomes Quality Initiative (KDOQI) recommends ing staining for IgG, IgA, IgM, C3, and C1q; and elec-
substituting a spot urine protein/creatinine ratio (PCR) tron microscopy.
assessment for 24-h urine testing [7, 10]. Several studies IgAN was diagnosed based on light microscopic find-
validating spot urine PCR in patients with chronic kid- ings of mesangial proliferative changes, immunofluores-
ney diseases (CKD) or normal kidney function have been cence findings of mesangial IgA and C3 deposition, and
conducted [5, 11, 12]. However, studies on the associ- electron microscopic findings of electron-dense deposits
ation between a spot urine PCR and 24-h urine protein in the mesangial area [13].
(24HP) in patients with chronic glomerular nephritis No abnormalities of kidney tissue on light microscopy
(CGN) and nephrotic syndrome (NS) are limited. were found in patients with MCD. However, podocyte
This study aimed to evaluate the correlation and damage was found on electron microscopy [14].
agreement between spot urine PCR with urine protein In MN-NS, diagnostic features included capillary wall
excretion measured by 24 h urinary collection in patients thickening, normal cellularity, IgG and C3 found along
with CGN and NS. the capillary walls upon immunofluorescence, and sube-
pithelial deposits visible on electron microscopy [15].
Methods There were no patients with the pathological features
Patient population of diabetic nephropathy.
The study participants included 161 patients with im-
munoglobulin A nephropathy (IgAN), minimal change Ethical committee
disease (MCD), or membranous nephropathy –nephrotic The study protocol was approved by the ethical com-
syndrome (MN-NS) and who were diagnosed through mittee of the Jikei University Kashiwa Hospital and
kidney biopsy at the Jikei University Kashiwa Hospital Kanagawa Prefecture Shiomidai Hospital. Informed
and Kanagawa Prefecture Shiomidai Hospital between consent was not obtained from an individual patient,
2008 and 2015. because their laboratory data used in this study were
Patients with diabetes mellitus or taking renin-angio- extracted from routine examinations files and ana-
tensin-aldosterone system inhibitors were excluded, be- lyzed retrospectively. However, we posted the research
cause the amount of proteinuria could be influenced by content at each hospital and given the opportunity to
the treatments of underlying disease. refuse to participate in this research.

Data collection Statistical analysis

Clinical and laboratory information Data are expressed as numbers (%), means (standard
Data on baseline demographics and clinical and labora- deviation) or median (25th percentile, 75th percentile).
tory data were reviewed prior to renal biopsy. Age, sex, Based on previous studies, we considered a 500 mg
body weight, body mass index (BMI), and body surface difference in proteinuria as clinically meaningful when
area were obtained from each medical chart. Serum estimating 24HP using spot urine PCR. We calculated
creatinine (Cr) levels were measured by routine methods that with a sample of 126 patients, the study would have
(enzyme assay; CRE-II, Kainos Laboratory Inc., Tokyo, 80% power to detect a 500 mg mean difference in
Kobayashi et al. BMC Nephrology (2019) 20:306 Page 3 of 7

proteinuria, with a type 1 error of 5%. For power ana- Results

lysis, we used a standard division of 750 mg [16]. The patients’ characteristics are shown in Table 1. In this
The difference of the mean value between the three study, 84, 53, and 24 patients had IgAN, MCD, and
groups was assessed using analysis of variance (ANOVA). MN-NS, respectively. The mean age was 44.9 ± 18.9
Categorical data were tested by the chi-square test. Vari- years, and 56.5% of the patients were male. The patients
ables without normality of data distribution were tested by with MN-NS were older than the others.
the Mann-Whiney U test. The correlation between spot There were no body weight, BMI, and body surface
urine PCR and a 24HP was investigated using linear area differences among each group.
regression analysis with Spearman’s correlation coefficient Among all patients, the mean serum Cr was 1.10 ±
(r) and the agreement was assessed by intraclass correl- 0.87 mg/dL, and eGFR was 69.8 ± 27.6 mL/min/1.73 m2.
ation coefficient (ICC). The Cohen’s kappa coefficient (κ) The patients with MCD had a higher level of serum Cr
was also calculated to evaluate the consistency between and lower level of eGFR than the others. There was no
spot urine PCR and a 24 HP, in which spot urine 24-h urinary creatinine differences among each group
PCR (g/gCre) and a 24 HP (g/day) were classified as (P = 0.06). The median 24HP value was 3.64 g/day, and
≤0.5, 0.5–1.0, 1.0–3.5 and ≥ 3.5. the patients with MCD and MN-NS had higher levels of
In general, the following regression coefficients were 24HP than the patients with IgAN. The median spot
obtained: 0.7–1.0, for strong correlation; 0.4–0.7, for PCR was 2.99, and the value of spot PCR in patients
slight correlation; 0.2–0.4, for weak correlation; 0–0.2, with MCD and MN-NS was higher than that in patients
for almost no correlation. In the case of ICC evaluation with IgAN.
score, 0.20 was considered slight, 0.21–0.40, fairer; 0.41– A strong correlation between 24HP and spot urine
0.60, moderate; 0.61–0.80, substantial; and 0.81, almost PCR in all cases (r = 0.9, P < 0.001) and substantial agree-
perfect. And κ was used to define the level of agree- ment in all cases (ICC: 0.73, 95% confidence interval
ment obtained: κ < 0, poor agreement; κ = 0–0.20, (95% CI): 0.649–0.795, P < 0.001) were found as shown
minimal agreement; κ = 0.21–0.40, fair agreement; in Table 2. In patients with IgAN, a strong correlation
0.41–0.60, moderate agreement; 0.61–0.80, substantial (r = 0.86, P < 0.001) and substantial agreement (ICC =
agreement; and 0.81–1, almost perfect or perfect 0.806, 95% CI: 0.713–0.871, P < 0.001) were found in all
agreement. cases (Table 2, Fig. 1b). However, in the patients with
The 24HP and mean differences between the results of MCD, r was 0.53 (P < 0.001), which was considered as
24HP and spot urine PCR were assessed using Bland– slight correlation, and ICC was 0.42 (95% CI: 0.174–
Altman analysis ((A) all patients, (B) IgAN, (C) MCD, 0.617, P = 0.001), which was considered to have moder-
and (D) MN-NS). The limits of agreement for each com- ate agreement (Table 2, Fig. 1c). In the patients with
parison are indicated by the average difference ± 1.96 MN-NS, r was 0.289 (P = 0.17), and ICC was 0.08 (95%
standard deviations of the difference. CI: − 0.306–0.454, P = 0.346), which were not statistically
A two-sided p value of 0.05 was considered statisti- significant (Table 2, Fig. 1d).
cally significant. Statistical analysis was performed Same trend was also ensured by method agreement
using the IBM SPSS version 18 software (IBM Corp., analysis employing κ coefficient. While among all pa-
Armonk, NY, USA). tients, the substantial agreement was recognized (κ: 0.63,

Table 1 Patients’ characteristics

All cases IgAN MCD MGN-NS N = 24 P values
N = 161 N = 84 N = 53 (by ANOVA)
Age, years 44.9 ± 18.9 40.0 ± 15.9 43.5 ± 20.3 65.0 ± 10.8 < 0.001
Male, n (%) 91 (56.5) 43 (51.2) 31 (58.5) 17 (70.8) 0.217
Creatinine, mg/dL 1.10 ± 0.87 0.95 ± 0.40 1.32 ± 1.30 1.11 ± 0.84 0.051
2
eGFR, mL/min/1,73 m 69.8 ± 27.6 72.2 ± 24.9 69.1 ± 32.5 62.7 ± 24.5 0.326
Spot urinary protein, mg/dL 749 ± 1148 129 ± 152 1506 ± 1315 1249 ± 1483 < 0.001
Spot urinary creatinine, mg/dL 151 ± 125 115 ± 93 207 ± 155 153 ± 110 < 0.001
24-h urinary creatinine, g/day 1.17 ± 0.47 1.23 ± 0.4 1.16 ± 0.49 1.00 ± 0.29 0.1
24-h urinary protein, mg/dL 466 ± 704 84 ± 92 1028 ± 867 560 ± 668 < 0.001
Daily urinary protein, g/day 4.32 ± 4.51 1.22 ± 1.24 8.44 ± 4.88 6.00 ± 2.29 < 0.001
24-h urine volume, mL/day 1502 ± 769 1655 ± 711 1242 ± 809 1537 ± 750 0.008
Data are expressed as means ± standard deviation or numbers (%). IgAN denotes immunoglobulin A nephropathy, MCD minimal change disease, MGN-NS
Membranous glomerulonephritis with nephrotic syndrome, ANOVA analysis of variance, eGFR estimated glomerular filtration rate
Kobayashi et al. BMC Nephrology (2019) 20:306 Page 4 of 7

Table 2 Correlation between spot urinary protein creatinine ratio and 24-h proteinuria
All cases IgAN MCD MGN-NS
N = 161 N = 84 N = 53 N = 24
Pearson’s correlation coefficient (r) 0.734 0.827 0.628 0.092
P values <0.001 <0.001 0.001 0.670
Intraclass correlation coefficient (ICC) 0.730 0.806 0.420 0.080
(95% confidential interval) (0.649–0.795) (0.713–0.871) (0.174–0.617) (- 0.306–0.454)
P values <0.001 <0.001 0.001 0.346
IgAN denotes immunoglobulin A nephropathy, MCD minimal change disease, MGN-NS Membranous glomerulonephritis with nephrotic syndrome

P < 0.001), among the patients with IgAN, κ was 0.51 Discussion
(P < 0.001) which was considered to have a moderate Measurement of urinary protein excretion is a widely
agreement. However, in the case of patients with MCD, accepted method in the detection, diagnosis, and man-
κ was 0.22 (P = 0.01), which was considered to have an agement of people considered to be at risk for develop-
only fair agreement and in the case of patients with ing kidney disease and has been advocated as part of a
MN-NS, κ was − 0.07 (P = 0.65), which was considered regular check-up in such individuals [1–3, 17, 18].
to have no agreement. Recently, spot urine PCR has been used as a surrogate
Bland-Altman analysis investigating the association be- of the measurement of 24HP in the clinical practice.
tween 24HP and difference between a 24HP and spot However, in patients with CGN and NS, the correlation
urine PCR are shown in Fig. 2a-d. Significant bias was and agreement between spot PCR and 24HP have not
not observed in patients with IgAN. The higher the been fully elucidated [16, 19, 20]. This study aimed to
average volume of proteinuria, the higher the difference evaluate the difference of daily urine protein excretion
between the measured and estimated results on spot measured by 24HP and spot urine PCR in patients with
urine PCR assessment. CGN and NS. Our study showed that in IgAN, spot

a b

c d

Fig. 1 Correlation between spot urinary protein creatinine ratio and daily urinary protein. a: All cases (n = 161). There is a substantial correlation in
all cases (r = 0.9). b: IgAN cases (n = 84). A strong correlation is recognized in IgAN cases (r = 0.86). c: MCD cases (n = 53). A slight correlation is
found in MCD cases (r = 0.53). d: MN-NS cases (n = 24). No significant correlation is found in MN-NS cases (r = 0.289)
Kobayashi et al. BMC Nephrology (2019) 20:306 Page 5 of 7

a b

c d

Fig. 2 Bland-Altman analysis of the difference between 24-h urinary protein measured by spot urine PCR of all patients (a), IgAN (b), MCD (c),
and MN-NS (d)

urine PCR had a strong correlation with 24HP value. with preeclampsia, for severe proteinuria, a urine PCR of
However, similar results were not found in both MCD ≥5000 mg/g had a poor positive predictive value (61.9%)
and MGN-NS. and sensitivity (72.2%) [26], while other few studies have
The major finding of our study is that in patients with shown that a spot urine PCR and 24HP in patients with
IgAN, a strong correlation was found between spot urine high levels of protein in urine are related [27]. The previ-
PCR and 24HP value. Several previous studies showed ous study showed that even when a large amount of
this correlation in patients with CKD or normal kidney protein in urine is observed in nephrotic syndrome, the
function [6, 11, 21, 22]. However, only a few studies fo- coincidence rate is 89 to 94% [27]. The reason for these
cused on IgAN to investigate the association [23, 24]. inconsistencies needs to be fully elucidated; however, pre-
Among patients with glomerulonephritis in this cross- vious results differed with regard to age, race, country,
sectional study, high correlation coefficients (r = 0.91, timing of a spot urine, and patients’ diseases.
95% CI: 0.95–0.98) were observed [23]. In addition, in a Several reasons can be considered why a spot urine
cohort study of 182 selected patients with primary IgAN, PCR is reliable for 24HP in patients with IgAN, but
a good correlation was found between urine albumin-to- unreliable in patients with MCD or MN-NS. Megalin
creatinine ratio and 24HP, except those pertaining to may play an important role in our findings. Megalin,
CKD stage 5, in patients with IgAN [24]. In the current which is known as a low-density lipoprotein-related
study, similar results were observed. protein, is one of the large transmembrane proteins
Another major finding of our study is that among pa- expressed on the surface of proximal tubular epithelial
tients with MCD or MGN-NS, who had nephrotic-range cells, where they are central to the endocytic reabsorp-
proteinuria, poor or no correlation was found between a tion of many plasma proteins filtered across the glom-
spot urine PCR and 24HP value. Until recently, few erular capillary wall [28–30]. Owing to reabsorption of
studies investigating the association between spot urine protein in urine by megalin, patients with normal kidney
PCR and 24HP in patients with NS, mainly focused on function have very limited amount of proteins in urine.
preeclampsia. However, in nephrotic-range diseases such as MCD or
Some studies showed that in patients with nephrotic- MN-NS, the mechanism behind these observations re-
range proteinuria, this association was not related [25, 26]. mains unclear. Previous studies showed that deficiency
Previous observational studies demonstrated that the ran- of megalin is likely to be associated with the develop-
dom urine albumin/creatinine ratio was a poor predictor ment of proteinuria/albuminuria and increased urinary
for a proteinuria of > 2 g/day in patients with preeclampsia megalin excretion is associated with tissue damage [31–33].
[25]. Another study investigated that among 220 women Ogasawara et al. suggested that urinary C-megalin levels
Kobayashi et al. BMC Nephrology (2019) 20:306 Page 6 of 7

were significantly high in patients with normoalbuminuria, Authors’ contributions

were elevated in line with increased albuminuria, and re- SK: Study conception, Manuscript preparation, HA: Analysis, Methodology,
Manuscript preparation, HT: Analysis, Revision, MO: Revision, Supervision, YK:
duced kidney function [33]. In nephrotic-range disease, we Revision, Supervision, TY: Project administration, Supervision. All authors have
hypothesized that the causes why spot urine PCR was not read and approved the manuscript and ensure that this is the case.
associated with 24HP were as follows: In nephrotic syn-
drome, kidney function may decrease because of causes Funding
No funding.
such as dehydration, and increase of sodium reabsorption
[14]; as a result, megalin function declines, affecting its role Availability of data and materials
in the reabsorption of proteins in urine (2). In excessive The datasets generated and analyzed during the study are not publicly
available due the terms of consent to which the participants agreed, but the
protein excretion, variations occurred in megalin reabsorp-
datasets generated and/or analyzed during the current study are available
tion. Therefore, the fluctuations in spot urine PCR alone upon request from the corresponding author.
were small; however, as the 24HP increased, the fluctua-
tions in spot urine PCR also increased [27]. We demon- Ethics approval and consent to participate
The study protocols conformed to the provisions of the Declaration of
strated that when nephrotic-range proteinuria was present, Helsinki and was approved by the ethical committee of the Jikei University
there was less actual predictive value between a spot urine Kashiwa Hospital (Approval number 7058) and Kanagawa Prefecture
PCR and 24HP. Future studies are warranted to investigate Shiomidai Hospital (Approval number 2706).
Written informed consent for participation was waived because of the
the association according to the amount of proteinuria retrospective nature of the study.
difference.
This study had several limitations. First, the findings Consent for publication
cannot be generalized to other ethnic or age groups, be- Not applicable.
cause the subjects were only eligible patients in the core
Competing interests
hospitals. However, because the core hospitals included The authors declare that they have no competing interests.
a university hospital and a prefectural hospital in differ-
ent prefectures in Japan, our study may be validated. Author details
1
Division of Nephrology and Hypertension, Department of Internal Medicine,
Second, we studied only the correlation of one sample The Jikei University School of Medicine, Tokyo, Japan. 2Department of Allergy
both from 24HP value and spot urine PCR. Moreover, and Rheumatology, Nippon Medical School Graduate School of Medicine,
our results were not demonstrated in other populations; Tokyo, Japan. 3Graduate School of Public Health, Teikyo University, Tokyo,
Japan. 4Department of Internal Medicine, Nephrology Teikyo University
therefore, external validity might not be proved. Third, School of Medicine Teikyo University Chiba Medical Center, Ichihara, Chiba,
there was also the possibility of sampling error when Japan.
collecting the 24-h urine sample. Generally, it is said
Received: 9 July 2018 Accepted: 23 July 2019
that 24 h urine Cr excretion is 1 g/day. In each group,
24 h urine Cr excretion was more 1 g/day and there was
no difference among each group. Therefore, the validity References
of collecting 24-h urine is considered to be reasonable. 1. Irie F, Iso H, Sairenchi T, Fukasawa N, Yamagishi K, Ikehara S, et al. The
relationships of proteinuria, serum creatinine, glomerular filtration rate with
cardiovascular disease mortality in Japanese general population. Kidney Int.
2006;69(7):1264–71.
Conclusions 2. Iseki K, Iseki C, Ikemiya Y, Fukiyama K. Risk of developing end-stage renal
disease in a cohort of mass screening. Kidney Int. 1996;49(3):800–5.
We demonstrated the strong correlation with 24HP value 3. Japanese Society of Nephrology. Evidence-based practice guideline for the
and a spot urine PCR in patients with IgAN. A spot urine treatment of CKD. Jpn J Nephrol. 2013;55:585–860.
PCR is reliable with 24HP in patients with IgAN. In con- 4. Ruilope LM, van Veldhuisen DJ, Ritz E, Luscher TF. Renal function: the
Cinderella of cardiovascular risk profile. J Am Coll Cardiol. 2001;38:1782–7.
trast, in patients with MCD and MN-NS, clinicians should 5. Shoji T, Abe T, Matsuo H, Egusa G, Yamasaki Y, Kashihara N, et al.
understand that difference should be considered in the Committee of Renal and Peripheral Arteries, Japan atherosclerosis society.
calculation of the amount of daily urinary protein excre- Chronic kidney disease, dyslipidemia, and atherosclerosis. J Atheroscler
Thromb. 2012;19:299–315.
tion between 24HP and a spot urine PCR. 6. Wilmer WA, Rovin BH, Hebert CJ, Rao SV, Kumor K, Hebert LA. Management
of glomerular proteinuria: a commentary. J Am Soc Nephrol. 2003;14(12):
3217–32.
Abbreviations 7. Ginsberg JM, Chang BS, Matarese RA, Garella S. Use of single voided urine
24HP: 24-h proteinuria; ICC: Intraclass correlation coefficient; samples to estimate quantitative proteinuria. N Engl J Med. 1983;309(25):
IgAN: Immunoglobulin A nephropathy; MCD: Minimal change disease; MGN- 1543–6.
NS: Membranous glomerulonephritis with nephrotic syndrome; PCR: Protein/ 8. Sekiguchi J, Teruya K, Horii K, Kuroda E, Konosaki H, Mizuguchi Y, et al.
creatinine ratio; r: Spearman’s correlation Molecular epidemiology of outbreaks and containment of drug-resistant
Pseudomonas aeruginosa in a Tokyo hospital. J Infect Chemother. 2007;
13(6):418–22 Epub 2007 Dec 25.
Acknowledgments 9. Nagao M, Iinuma Y, Igawa J, Saito T, Yamashita K, Kondo T, et al. Control of
We thank all staff, who was part of The Jikei University School of Medicine or an outbreak of carbapenem-resistant Pseudomonas aeruginosa in a
Kanagawa Prefecture Shiomidai Hospital, for their comments and technical haemato-oncology unit. J Hosp Infect. 2011;79(1):49–53. https://doi.org/10.1
assistance. 016/j.jhin.2011.04.018 Epub 2011 Jun 30.
Kobayashi et al. BMC Nephrology (2019) 20:306 Page 7 of 7

10. National Kidney Foundation. KDOQI clinical practice guidelines on with microalbuminuria and clinical diabetic nephropathy. Acta Diabetol.
hypertension and antihypertensive agents in chronic kidney disease. Am J 1992;28(3–4):206–10.
Kidney Dis. 2004;43:S1–S290. 32. Hong CY, Hughes K, Chia KS, Ng V, Ling SL. Urinary alpha1-microglobulin as
11. Schwab SJ, Christensen RL, Dougherty K, Klahr S. Quantitation of proteinuria a marker of nephropathy in type 2 diabetic Asian subjects in Singapore.
by the use of protein-to-creatinine ratios in single urine samples. Arch Diabetes Care. 2003;26(2):338–42.
Intern Med. 1987;147(5):943–4. 33. Ogasawara S, Hosojima M, Kaseda R, Kabasawa H, Yamamoto-Kabasawa K,
12. Ruggenenti P, Gaspari F, Perna A, Remuzzi G. Cross sectional Kurosawa H, et al. Significance of urinary full-length and ectodomain forms of
longitudinal study of spot morning urine protein:creatinine ratio, 24 megalin in patients with type 2 diabetes. Diabetes Care. 2012;35(5):1112–8.
hour urine protein excretion rate, glomerular filtration rate, and end
stage renal failure in chronic renal disease in patients without diabetes.
BMJ. 1998;316(7130):504–9. Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in
13. Yuzawa Y, Yamamoto R, Takahashi K, Katafuchi R, Tomita M, Fujigaki Y, et al.
published maps and institutional affiliations.
Evidence-based clinical practice guidelines for IgA nephropathy 2014. Clin
Exp Nephrol. 2016;20(4):511–35.
14. Nishi S, Ubara Y, Utsunomiya Y, Okada K, Obata Y, Kai H, et al. Evidence-
based clinical practice guidelines for nephrotic syndrome 2014. Clin Exp
Nephrol. 2016;20(3):342–70.
15. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis
Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis. 2012;
2:1–274.
16. Hogan MC, Reich HN, Nelson PJ, Adler SG, Cattran DC, Appel GB, et al. The
relatively poor correlation between random and 24-hour urine protein
excretion in patients with biopsy-proven glomerular diseases. Kidney Int.
2016;90(5):1080–9.
17. Levey AS, de Jong PE, Coresh J, El Nahas M, Astor BC, Matsushita K, et al.
The definition, classification, and prognosis of chronic kidney disease: a
KDIGO controversies conference report. Kidney Int. 2011;80(1):17–28.
18. Fox CS, Larson MG, Leip EP, Culleton B, Wilson PW, Levy D. Predictors of
new-onset kidney disease in a community-based population. JAMA. 2004;
291(7):844–50.
19. Price CP, Newall RG, Boyd JC. Use of protein:creatinine ratio measurements
on random urine samples for prediction of significant proteinuria: a
systematic review. Clin Chem. 2005;5(3):1577–86.
20. Ubukata M, Takei T, Nitta K. Estimation of the 24-h urinary protein excretion
based on the estimated urinary creatinine output. Clin Exp Nephrol. 2016;
20(5):456–61.
21. Xin G, Wang M, Jiao LL, Xu GB, Wang HY. Protein-to-creatinine ratio in spot
urine samples as a predictor of quantitation of proteinuria. Clin Chim Acta.
2004;350(1–2):35–9.
22. Birmingham DJ, Rovin BH, Shidham G, Nagaraja HN, Zou X, Bissell M, et al.
Spot urine protein/creatinine ratios are unreliable estimates of 24 h
proteinuria in most systemic lupus erythematosus nephritis flares. Kidney
Int. 2007;72(7):865–70.
23. Morales JV, Weber R, Wagner MB, Barros EJ. Is morning urinary protein/
creatinine ratio a reliable estimator of 24-hour proteinuria in patients with
glomerulonephritis and different levels of renal function? J Nephrol. 2004;
17(5):666–72.
24. Huan L, Yuezhong L, Chao W, HaiTao T. The urine albumin-to-creatinine
ratio is a reliable indicator for evaluating complications of chronic kidney
disease and progression in IgA nephropathy in China. Clinics (Sao Paulo).
2016;71(5):243–50.
25. Al RA, Borekci B, Yapca O, Keles S, Kadanali S. Albumin/creatinine ratio for
prediction of 24-hour albumin excretion of > or =2 g in manifest
preeclampsia. Clin Exp Obstet Gynecol. 2009;36(3):169–72.
26. Durnwald C, Mercer B. A prospective comparison of total protein/creatinine
ratio versus 24-hour urine protein in women with suspected preeclampsia.
Am J Obstet Gynecol. 2003;189(3):848–52.
27. NJ MI, Taal MW. To examine the use of urine total protein compared with
albumin measurements to assess and monitor patients with chronic kidney
disease. Curr Opin Nephrol Hypertens. 2008;17(6):600–3.
28. Saito A, Pietromonaco S, Loo AK, Farquhar MG. Complete cloning and
sequencing of rat gp330/"megalin," a distinctive member of the low density
lipoprotein receptor gene family. Proc Natl Acad Sci U S A. 1994;91(21):
9725–9.
29. Christensen EI, Birn H. Megalin and cubilin: multifunctional endocytic
receptors. Nat Rev Mol Cell Biol. 2002;3:256–66.
30. Saito A, Sato H, Iino N, Takeda T. Molecular mechanisms of receptor-
mediated endocytosis in the renal proximal tubular epithelium. J Biomed
Biotechnol. 2010;2010:403272.
31. Pontuch P, Jensen T, Deckert T, Ondrejka P, Mikulecky M. Urinary excretion
of retinol-binding protein in type 1 (insulin-dependent) diabetic patients