How do you accurately estimate renal function in bedbound patients with extremely low serum creatinine?

Comment by InpharmD Researcher

While there were no studies or guidance directly related to measurement of renal function in bedridden patients, one study found the most accurate Cockcroft-Gault estimate was obtained by adding 0.2 mg/dL to enzymatically measured creatinine to approximate Jaffe values, which gave 75.6% of estimates within ±30% of measured 24-hour creatinine clearance and minimal bias. However, creatinine-based GFR is unreliable and tends to overestimate renal function in patients with spinal cord injury/SMID who are stationary or bedridden, so cystatin C-based eGFR may be preferred when available.

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Background

A 2018 study investigated optimal adjustment protocols for serum creatinine (SCr) values to accurately reflect renal function in bedridden elderly patients. The researchers enrolled 45 hospitalized patients aged 65 years or older who were bedridden, with a mean age of 81.9 ± 8.2 years, and measured their 24-hour creatinine clearance (mCCr) via urine collection using an indwelling bladder catheter to ensure accuracy. Estimated creatinine clearance (eCCr) was calculated utilizing the Cockcroft-Gault (CG) formula based on enzymatically measured SCr values adjusted by five distinct methods: (a) using the actual enzymatic SCr without adjustment; (b) adding 0.2 mg/dL to approximate the Jaffe method values (+0.2 correction method); (c) rounding up values below 0.06 mmol/L to 0.06 mmol/L (Dooley method); (d) adjusting values below 1.0 mg/dL to 1.0 mg/dL (Smythe method); and (e) adjusting to 0.8 mg/dL for males and 0.6 mg/dL for females if below these thresholds (Furukubo method). [1]

Results demonstrated significant positive correlations between mCCr and eCCr across all methods (p<0.0005), with the highest correlation coefficients observed with the enzymatic method (R²= 0.75) and the +0.2 correction method (R²= 0.71). However, mean eCCr values differed significantly from mCCr in the enzymatic and Smythe groups, indicating overestimation and underestimation of renal function, respectively. Bland-Altman analyses revealed minimal bias and better precision in the +0.2 correction, Dooley, and Furukubo groups, while the Smythe method exhibited a proportional bias and lower agreement. Prediction accuracy, defined as the percentage of patients with eCCr within ±30% of mCCr, was highest at 75.6% using the +0.2 correction method, followed by 71.1% with the Dooley method. These findings suggest that adjusting enzymatic SCr values by adding 0.2 mg/dL to approximate Jaffe assay results yields the most accurate eCCr estimates in bedridden elderly patients, improving assessment of renal function necessary for optimized drug dosing. [1]

Background References: [1] Otani T, Kase Y, Kunitomo K, et al. What is the correct adjustment protocol for serum creatinine value to reflect renal function in bedridden elderly patients? Jpn J Nephrol Pharmacother. 2018;7(1):3-12. Accessed October 17, 2026. https://www.jstage.jst.go.jp/article/jjnp/7/1/7_3/_pdf
Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

How do you accurately estimate renal function in bedbound patients with extremely low serum creatinine?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→


Please see Tables 1-2 for your response.

Assessment of renal function in persons with motor complete spinal cord injury—cystatin C as an accurate single marker
Design

Observational cohort study

N= 30
Objective To assess if Cystatin C is an accurate marker for estimating GFR in persons with SCI with no preserved motor power and to study if the use of Serum creatinine for estimation of GFR in this population significantly overestimates GFR
Study Groups All participants (n= 30)
Inclusion Criteria ASIA A and ASIA B according to American Spinal Injury Association Impairment Scale; Age 18 years to 60 years; More than 6 months post injury
Exclusion Criteria ASIA C and ASIA D; Less than 6 months post injury; Known thyroid disease; Age less than 18 years or more than 60 years; Pregnancy and lactation
Methods Serum Creatinine and Serum Cystatin C values were obtained, and eGFR was calculated based on available formulae. 24-h urine for urine creatinine clearance-based eGFR was used as a reference value. Bland-Altman plot method was used for analysis.
Duration Data collection over a period of 1 year
Outcome Measures

Primary: Accuracy of Cystatin C as a single marker for GFR estimation

Secondary: Overestimation of GFR using Serum Creatinine
Baseline Characteristics   All patients (n= 30)
Mean age, years (SD) 33.8 (9.43)
Male 29 (96.7%)
Female 1 (3.3%)
Tetraplegia 6 (20%)
Paraplegia 24 (80%)
ASIA A 25 (83.3%)
ASIA B 5 (16.7%)
Indwelling urethral catheter 40%
Self Intermitted Clean Catheterisation 50%
Suprapubic indwelling catheter 10%
Results   Mean Difference from Reference GFR (%)
Serum Creatinine CKD-EPI 50.6%
Creatinine Cockcroft Gault 45.09%
Cystatin C CKD-EPI -0.47%
Combined Cystatin C and Creatinine CKD-EPI 19.76%
Adverse Events No adverse events reported
Study Author Conclusions Cystatin C is an accurate single marker for GFR estimation in individuals with motor complete SCI. Using serum creatinine to estimate GFR significantly overestimates GFR and is not recommended for clinical practice.
Critique The study provides valuable insights into the accuracy of Cystatin C as a marker for GFR estimation in SCI patients, highlighting its potential over serum creatinine. However, the small sample size and single-center design may limit the generalizability of the findings. Additionally, the lack of a gold standard for GFR measurement could affect the robustness of the conclusions.

 

Table 1 References:
[2] Augustine TA, M HP, Alexander S, S MG. Assessment of renal function in persons with motor complete spinal cord injury-cystatin C as an accurate single marker. Spinal Cord. 2024;62(6):295-299. doi:10.1038/s41393-024-00973-y
Evaluation of eGFRs to Calculate Kidney Function in Adults with Severe Motor and Intellectual Disabilities
Design

Retrospective study

N= 18
Objective To evaluate and compare the efficacy of eGFR formulas using serum creatinine, cystatin C, and beta-2 microglobulin in patients with severe motor and intellectual disabilities (SMID)
Study Groups All patients (n= 18)
Inclusion Criteria SMID patients who underwent 24-h creatinine clearance (Ccr) for clinical reasons between September 2021 and June 2023
Exclusion Criteria None specified
Methods

The study used three eGFR formulas: Cr-based, cysC-based, and β2MG-based. eGFR-Ccr was obtained from 24-h urine collection. Statistical analyses included mean error (ME), root mean square error (RMSE), and P30 to compare eGFR values with eGFR-Ccr.
Duration September 2021 to June 2023
Outcome Measures

Primary: Reliability and validity of eGFR formulas compared to eGFR-Ccr

Secondary: None specified
Baseline Characteristics   All patients (n= 18)
Sex - Male 10
Sex - Female 8
Age 20~39 years 9
Age 40~59 years 7
Age 60~79 years 2
Underlying disease - Cerebral palsy 10
Underlying disease - Congenital brain damage 3
Underlying disease - Brain malformation 2
Underlying disease - CNS infection sequelae 1
Underlying disease - Other 2
Results   eGFR-Cr eGFR-cysC eGFR-β2MG
Mean Error (ME) (mL/min/1.73 m2) 74.5 2.3 6.5
Root Mean Square Error (RMSE) (mL/min/1.73 m2) 92.3 25.7 33.4
P30 (%) 16.7 77.8 72.2
Adverse Events None reported
Study Author Conclusions

eGFR-Cr is not recommended for assessing kidney function in SMID patients due to overestimation. eGFR-cysC is more reliable for evaluating kidney function in this population.
Critique

The study is limited by its small sample size and retrospective design. The use of eGFR-Ccr instead of the gold standard Cin may affect the accuracy of the findings. However, the study provides valuable insights into the assessment of kidney function in SMID patients, highlighting the limitations of creatinine-based eGFR in this population.

 

Table 2 References:
[3] Uemura O, Hasegawa Y, Nakashima H, Otobe Y. Evaluation of eGFRs to Calculate Kidney Function in Adults with Severe Motor and Intellectual Disabilities. JMA J. 2023;6(4):481-486. doi:10.31662/jmaj.2023-0069