Biostatistics utilities for nephrology

Description

Set of tools for the estimation of kidney function and related traits.

Included are the following glomerular filtration rate (GFR) estimating functions: the Modification of Diet in Renal Disease (MDRD) study equations based on four (MDRD4) or six (MDRD6) parameters (Levey 1999; Levey 2006); the CKD-Epi equations for serum creatinine with the race coefficient (CKDEpi.creat) and without the race coefficient (CKDEpi2021.creat); the CKD-Epi equation for cystatin C (CKDEpi.cys); the CKD-Epi equation for the combination of creatinine and cystatin C with (CKDEpi.creat.cys) and without (CKDEpi2021.creat.cys) the race coefficient (Inker 2012; Inker 2021); the three equations proposed by Stevens 2008 based on cystatin C only (Stevens.cys1), age- and sex-weighted cystatin C (Stevens.cys2), and a combination of cystatin C and creatinine (Stevens.creat.cys); the classic Cockroft and Gault 1976 equation for creatinine clearance estimation (CG); the equation by Virga (2007) (Virga); the race-free equations developed by the European Kidney Function Consortium (EKFC) including sex and age based on serum creatinine (EKFC.creat) (Pottel 2021) and based on serum cystatin C with (EKFC.cys) and without (EKFC_SF.cys) the sex coefficient (Pottel 2023); the full age spectrum (FAS) equations using serum creatinine (FAS.creat) (Pottel 2016), cystatin C (FAS.cys), and their combination (FAS.creat.cys) (Pottel 2017); the Schwartz bedside formula (Schwartz.Bedside) (Schwartz 2009).

A comparative description of several GFR-estimating functions included in the initial version of the package can be found in Pattaro (2013). Extensive literature does exist that compares the methods described.

Additional serum biomarkers are the blood urea nitrogen (BUN)-to-creatinine ratio (BCR and the urea-to-creatinine ratio UCR.

Urine biomarkers included are the albumin-to-creatinine ratio UACR and the protein-to-creatinine ratio UPCR

Some unit conversion functions are provided to facilitate operations.

Details

Author(s)

Cristian Pattaro <cristian.pattaro@eurac.edu>, Ryosuke Fujii <ryosuke.fujii@eurac.edu>, Janina Herold <janina.herold@klinik.uni-regensburg.de>

Acknowledgements: Max Plischke, Joao Sabino, Xiao Jiang for bug reporting; Alexander Tolios, Thomas Winkler for input on the software package; Andrew Srisuwananukorn for contributing scripts; the 'nephro' user community for continuous feedback.

References

Citing this package:
- Pattaro C, Riegler P, Stifter G, Modenese M, Minelli C, Pramstaller PP. Estimating the glomerular filtration rate in the general population using different equations: effects on classification and association. Nephron Clin Pract 2013; 123(1-2):102-11.

Formulas:
- Cockroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31-41.
- Inker LA, et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med 2012; 367: 20-9.
- Inker LA, et al. New Creatinine- and Cystatin C-based Equations to Estimate GFR without Race. N Engl J Med 2021; 385: 1737-1749.
- Levey AS, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999; 130(6): 461-70.
- Levey AS, et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006; 145: 247-54.
- Stevens LA, et al. Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD. Am J Kidney Dis 2008; 51: 395-406.
- Virga G, et al. A new equation for estimating renal function using age, body weight and serum creatinine. Nephron Clin Pract 2007; 105: c43-53.
- Pottel H, et al. Development and Validation of a Modified Full Age Spectrum Creatinine-Based Equation to Estimate Glomerular Filtration Rate: A Cross-sectional Analysis of Pooled Data. Ann Intern Med 2021; 174: 183-191.
- Pottel H, et al. Cystatin C-Based Equation to Estimate GFR without the Inclusion of Race and Sex. N Engl J Med 2023; 388: 333-343.
- Pottel H, et al. An estimated glomerular filtration rate equation for the full age spectrum. Nephrol Dial Transplant 2016; 31:798-806.
- Pottel H, et al. Estimating glomerular filtration rate for the full age spectrum from serum creatinine and cystatin C Nephrol Dial Transplant 2017; 32: 497-507.
- Schwartz GJ, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol 2009; 20:629-637.

On IDMS calibration:
- Levey AS, et al. Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin Chem 2007; 53:766-72.
- Matsushita K, et al. Comparison of risk prediction using the CKD-EPI equation and the MDRD study equation for estimated glomerular filtration rate. J Am Med Assoc 2012; 307:1941-51.
- Skali H, et al. Prognostic assessment of estimated glomerular filtration rate by the new Chronic Kidney Disease Epidemiology Collaboration equation in comparison with the Modification of Diet in Renal Disease Study equation. Am Heart J 2011; 162:548-54.

Examples

# Comparison between different equations

creat <- c(0.8, 0.9, 1.0, 1.1, 1.2, 1.3)
cyst  <- c(1.1, 0.95, 1.1, 1.0, 1.3, 1.2)
sex <- c(1, 1, 1, 0, 0, 0)
age <- c(60, 65, 43, 82, 71, 55)
ethn <- round(runif(6))
wt <- c(70, 80, 60, 55, 87, 71)

eGFR <- data.frame(creat, cyst)
eGFR$MDRD4 <- MDRD4(creat, sex, age, ethn, 'IDMS')
eGFR$CKDEpi.creat <- CKDEpi.creat(creat, sex, age, ethn) 
eGFR$CKDEpi2021.creat <- CKDEpi2021.creat(creat, sex, age)
eGFR$CKDEpi.cys <- CKDEpi.cys(cyst, sex, age)
eGFR$CKDEpi.creat.cys <- CKDEpi.creat.cys(creat, cyst, sex, age, ethn)
eGFR$CKDEpi2021.creat.cys <- CKDEpi2021.creat.cys(creat, cyst, sex, age)
eGFR$Stevens.cys1 <- Stevens.cys1(cyst)
eGFR$Stevens.cys2 <- Stevens.cys2(cyst, sex, age, ethn)
eGFR$Stevens.creat.cys <- Stevens.creat.cys(creat, cyst, sex, age, ethn)
eGFR$cg <- CG(creat, sex, age, wt)
eGFR$virga <- Virga(creat, sex, age, wt)

pairs(eGFR[,3:13])

# For use with non-IDMS calibrated creatinine 
# several authors (see references) suggested
# a 5% creatinine adjustment

creat <- c(0.8, 0.9, 1.0, 1.1, 1.2, 1.3)
sex <- c(1, 1, 1, 0, 0, 0)
age <- c(60, 65, 43, 82, 71, 55)
ethn <- round(runif(6))
gfr <- CKDEpi.creat(0.95*creat, sex, age, ethn) 

BUN-to-creatinine ratio

Description

Calculate the plasma or serum BUN-to-creatinine ratio

Usage

BCR(BUN, creatinine) 

Arguments

Value

A numeric vector with BCR values.

Author(s)

Cristian Pattaro

References

Dossetor JB. Creatininemia Versus Uremia. The relative significance of blood urea nitrogen and serum creatinine concentrations in azotemia. Ann Int Med. 1966; 65(6): 1287-1299.

See Also

UCR

Cockroft and Gault equation

Description

Creatinine clearance is estimated with the Cockroft and Gault formula.

Usage

CG(creatinine, sex, age, wt)

Arguments

Value

A numeric vector with eGFR values in ml/min/1.73 m^2.

Author(s)

Cristian Pattaro

References

Cockroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31-41.

See Also

CKDEpi.creat, MDRD4, Virga

CKD-EPI equation for serum creatinine

Description

GFR is estimated with the CKD-EPI Study equation based on IDMS serum or plasma creatinine.

Usage

CKDEpi.creat(creatinine, sex, age, ethnicity)

Arguments

Value

A numeric vector with eGFR values in ml/min/1.73 m^2.

Author(s)

Cristian Pattaro

References

Inker LA, et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med 2012; 367: 20-29.

See Also

CKDEpi.creat.cys, CKDEpi.cys, CKDEpi2021.creat

CKD-EPI equation for creatinine and cystatin C

Description

CKD-EPI equation to estimate GFR based on a combination of creatinine and cystatin C

Usage

CKDEpi.creat.cys(creatinine, cystatin, sex, age, ethnicity)

Arguments

Value

A numeric vector with eGFR values in ml/min/1.73 m^2.

Author(s)

Cristian Pattaro

References

Inker LA, et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med 2012; 367: 20-29.

See Also

CKDEpi.creat, CKDEpi.cys, CKDEpi2021.creat.cys

CKD-EPI equation for cystatin C

Description

GFR is estimated with the CKD-EPI equation for cystatin C proposed by Inker et al., N Engl J Med 2012

Usage

CKDEpi.cys(cystatin, sex, age)

Arguments

Value

The function returns a numeric vector with eGFR values in ml/min/1.73 m^2.

Author(s)

Cristian Pattaro

References

Inker LA, et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med 2012; 367: 20-29.

See Also

CKDEpi.creat, CKDEpi.creat.cys

Race-free CKD-EPI equation for serum creatinine

Description

GFR is estimated with the CKD-EPI Study equation based on serum creatinine without the ethnicity coefficient.

Usage

CKDEpi2021.creat(creatinine, sex, age)

Arguments

Value

A numeric vector with eGFR values in ml/min/1.73 m^2.

Author(s)

Ryosuke Fujii

References

Inker LA, et al. New creatinine- and cystatin C-based equations to estimate GFR without race. N Engl J Med 2021; 385: 1737-1749.

See Also

CKDEpi.creat, CKDEpi.creat.cys, CKDEpi.cys, CKDEpi2021.creat.cys

Race-free CKD-EPI equation for serum creatinine and cystatin C

Description

CKD-EPI equation to estimate GFR based on a combination of creatinine and cystatin C without the ethnicity coefficient

Usage

CKDEpi2021.creat.cys(creatinine, cystatin, sex, age)

Arguments

Value

A numeric vector with eGFR values in ml/min/1.73 m^2.

Author(s)

Ryosuke Fujii

References

Inker LA, et al. New creatinine- and cystatin C-based equations to estimate GFR without race. N Engl J Med 2021; 385: 1737-1749.

See Also

CKDEpi.creat, CKDEpi.creat.cys, CKDEpi.cys, CKDEpi2021.creat

Convertion formula to change from mg/dL to mmol/L and vice versa

Description

mg/dL <–> mmol/L conversion

Usage

Convert.mgdL.mmolL(mg.dL, mmol.L)
## If your variable X is expressed in mg/dL, use: Convert.mgdL.mmolL(mg.dL=X)
## If your variable X is expressed in mmol/L, use: Convert.mgdL.mmolL(mmol.L=X)

Arguments

Value

A numeric vector with the converted values.

Author(s)

Cristian Pattaro

See Also

Convert.mgdL.umolL

Convertion formula to change from mg/dL to umol/L and vice versa

Description

mg/dL <–> umol/L conversion

Usage

Convert.mgdL.umolL(mg.dL, umol.L)
## If your variable X is expressed in mg/dL, use: Convert.mgdL.mmolL(mg.dL=X)
## If your variable X is expressed in umol/L, use: Convert.mgdL.mmolL(umol.L=X)

Arguments

Value

A numeric vector with the converted values.

Author(s)

Cristian Pattaro

See Also

Convert.mgdL.umolL

EKFC equation for serum creatinine

Description

EKFC equation for serum creatinine modified from FAS equation

Usage

EKFC.creat(creatinine, sex, age)

Arguments

Value

The function returns a numeric vector with eGFR values in ml/min/1.73 m^2.

Author(s)

Janina Herold

References

Pottel, H, et al. Development and Validation of a Modified Full Age Spectrum Creatinine-Based Equation to Estimate Glomerular Filtration Rate : A Cross-sectional Analysis of Pooled Data. N Engl J Med 2021; 174: 183-191.

See Also

EKFC.cys, CKDEpi.creat

EKFC equation for cystatin C

Description

EKFC equation for cystatin C that includes the sex coefficient, as proposed by Pottel et al., N Engl J Med 2023

Usage

EKFC.cys(cystatin, sex, age)

Arguments

Value

The function returns a numeric vector with eGFR values in ml/min/1.73 m^2.

Author(s)

Janina Herold

References

Pottel, H, et al. Cystatin C-Based Equation to Estimate GFR without the Inclusion of Race and Sex. N Engl J Med 2023; 388: 333-343.

See Also

EKFC_SF.cys

Sex-free EKFC equation for cystatin C

Description

EKFC equation for cystatin C without the sex coefficient as proposed by Pottel et al., N Engl J Med 2023

Usage

EKFC_SF.cys(cystatin, age)

Arguments

Value

The function returns a numeric vector with eGFR values in ml/min/1.73 m^2.

Author(s)

Janina Herold

References

Pottel, H, et al. Cystatin C-Based Equation to Estimate GFR without the Inclusion of Race and Sex. N Engl J Med 2023; 388: 333-343.

See Also

EKFC.cys

FAS equation for serum creatinine

Description

Full age spectrum (FAS) equation to estimate GFR based on serum creatinine

Usage

FAS.creat(creatinine, sex, age)

Arguments

Value

A numeric vector with eGFR values in ml/min/1.73 m^2.

Author(s)

Janina Herold

References

Pottel, H., et al. An estimated glomerular filtration rate equation for the full age spectrum. Nephrol Dial Transplant. 2016; 5: 798-806.

See Also

FAS.creat.cys, FAS.cys

FAS equation for creatinine and cystatin C

Description

Full age spectrum (FAS) GFR estimation based on serum creatinine and cystatin C

Usage

FAS.creat.cys(creatinine, cystatin, sex,age)

Arguments

Value

The function returns a numeric vector with eGFR values in ml/min/1.73 m^2.

Author(s)

Janina Herold

References

Pottel, H., et al. An estimated glomerular filtration rate equation for the full age spectrum from serum creatinine and cystatin C. Nephrol Dial Transplant. 2017; 32: 497-507.

See Also

FAS.cys

FAS equation for cystatin C

Description

Full age spectrum (FAS) GFR estimation based on cystatin C

Usage

FAS.cys(cystatin, sex, age)

Arguments

Value

A numeric vector with eGFR values in ml/min/1.73 m^2.

Author(s)

Janina Herold

References

Pottel, H., et al. An estimated glomerular filtration rate equation for the full age spectrum from serum creatinine and cystatin C. Nephrol Dial Transplant. 2017; 32: 497-507.

See Also

FAS.creat, FAS.creat.cys

Four-parameter MDRD study equation

Description

GFR is estimated with the 4-parameter Modification of Diet in Renal Disease (MDRD) study equation.

Usage

MDRD4(creatinine, sex, age, ethnicity, method = "IDMS")

Arguments

Value

A numeric vector with eGFR values in ml/min/1.73 m^2.

Author(s)

Cristian Pattaro

References

Levey AS, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999; 130(6): 461-70.
Levey AS, et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006; 145: 247-254.

See Also

CKDEpi.creat, MDRD6, CG

Six-parameter MDRD study equation

Description

GFR is estimated with the 6-parameter Modification of Diet in Renal Disease (MDRD) study equation.

Usage

MDRD6(creatinine, sex, age, albumin, BUN, ethnicity, method = 'IDMS')

Arguments

Value

A numeric vector with eGFR values in ml/min/1.73 m^2.

Author(s)

Cristian Pattaro

References

Levey AS, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999; 130(6): 461-70.
Levey AS, et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006; 145: 247-254.

See Also

MDRD4

Bedside IDMS-traceable Schwartz GFR Calculator for Children

Description

GFR is estimated with the Bedside Schwartz equation for Children based on IDMS serum or plasma creatinine.
This equation is valid in the 1-17 years age range.

Usage

Schwartz.Bedside(creatinine, ht, age)

Arguments

Value

A numeric vector with eGFR values in ml/min/1.73 m^2.

Author(s)

Andrew Srisuwananukorn

References

Schwartz GJ, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol 2009; 20: 629-637.

Stevens' formula for a combination of serum creatinine and cystatin C

Description

GFR estimation using the 3rd formula proposed by Stevens et al. (Am J Kidney Dis 2008), which combines creatinine and cystatin C

Usage

Stevens.creat.cys(creatinine, cystatin, sex, age, ethnicity)

Arguments

Value

The function returns a numeric vector with eGFR values in ml/min/1.73 m^2.

Author(s)

Cristian Pattaro

References

Stevens LA, et al. Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD. Am J Kidney Dis 2008; 51: 395-406.

See Also

CKDEpi.creat.cys

GFR estimation using serum cystatin C

Description

GFR is estimated with the 1st formula proposed by Stevens et al. (Am J Kidney Dis 2008), i.e.: as a simple transformation of cystatin C, without using any other information

Usage

Stevens.cys1(cystatin)

Arguments

Value

A numeric vector with eGFR values in ml/min/1.73 m^2.

Author(s)

Cristian Pattaro

References

Stevens LA, et al. Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD. Am J Kidney Dis 2008; 51: 395-406.

See Also

Stevens.cys2, Stevens.creat.cys, CKDEpi.cys

Stevens' formula for serum cystatin C, age, and sex

Description

GFR is estimated with the 2nd formula proposed by Stevens et al. (Am J Kidney Dis 2008), where cystatin C is weighted by sex and age

Usage

Stevens.cys2(cystatin, sex, age, ethnicity)

Arguments

Value

A numeric vector with eGFR values in ml/min/1.73 m^2.

Author(s)

Cristian Pattaro

References

Stevens LA, et al. Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD. Am J Kidney Dis 2008; 51: 395-406.

See Also

Stevens.cys1, Stevens.creat.cys, CKDEpi.cys

Urinary albumin-to-creatinine ratio

Description

Calculate the urinary albumin-to-creatinine ratio

Usage

UACR(u.albumin, u.creatinine) 

Arguments

Value

A numeric vector with UACR values.

Author(s)

Cristian Pattaro

References

Barratt TM, McLaine PN, Soothill JF. Albumin excretion as a measure of glomerular dysfunction in children. Arch Dis Child. 1970. 45(242): 496-501

See Also

UPCR

Urea-to-creatinine ratio

Description

Calculate the plasma or serum urea-to-creatinine ratio

Usage

UCR(urea, creatinine) 

Arguments

Value

A numeric vector with UCR values.

Author(s)

Cristian Pattaro

References

Kahn S, et al. The significance of serum creatinine and the blood urea/serum creatinine ratio in azotaemia S. Afr. Med. J. 1972; 46: 1828-1832.

See Also

BCR

Urinary protein-to-creatinine ratio

Description

Calculate the urinary protein-to-creatinine ratio

Usage

UPCR(u.protein, u.creatinine) 

Arguments

Value

A numeric vector with UPCR values.

Author(s)

Cristian Pattaro

See Also

UACR

Virga's formula

Description

Virga's formula is based on serum creatinine, sex, age, and body weight.

Usage

Virga(creatinine, sex, age, wt)

Arguments

Value

A numeric vector with eGFR values in ml/min/1.73 m^2

Author(s)

Cristian Pattaro

References

Virga G, et al. A new equation for estimating renal function using age, body weight and serum creatinine. Nephron Clin Pract 2007; 105: c43-53.

See Also

CG, MDRD4