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International Urology and Nephrology
Published in: International Urology and Nephrology 10/2023

Open Access 23-03-2023 | Diabetes | Nephrology - Original Paper

The association between renal hyperfiltration and mortality is not mediated by diabetes mellitus

Authors: Mounir Ould Setti, Ari Voutilainen, Leo Niskanen, Tomi-Pekka Tuomainen

Published in: International Urology and Nephrology | Issue 10/2023

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Abstract

Background

Renal hyperfiltration (RHF), recently established as a risk factor for mortality, is linked to current and subsequent diabetes mellitus (DM). DM could be seen as a mediator in the pathway between RHF and mortality. However, the mediating role of DM in the relationship between RHF and mortality is unclear.

Methods and results

Based on a cohort of 2682 Finnish men from the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) followed-up for 35 years, we evaluated the association between RHF and mortality, with DM as a mediator, following two methods: a classic mediation analysis approach, using Cox regression, and a counterfactual framework for mediation analysis, using g-computation, Cox regression, and logistic regression. RHF is associated with an increased risk of mortality. This association was not mediated by DM. Under a counterfactual framework and on a hazard ratio scale, RHF association with mortality had a total effect of 1.54 (95% confidence interval, 1.26–1.98) and a controlled direct effect of 1.66 (1.34–2.16).

Conclusion

An association between RHF and mortality risk, independent of DM, was established. RHF should be considered, managed, and followed-up as a mortality-associated condition, regardless of the status of DM. We suggest clinicians to consider including RHF screening in routine clinical care, especially diabetic care.
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Literature
1.
Christiansen JS, Gammelgaard J, Frandsen M, Parving HH (1981) Increased kidney size, glomerular filtration rate and renal plasma flow in short-term insulin-dependent diabetics. Diabetologia 20(4):451–456PubMedCrossRef
2.
Ditzel J, Junker K (1972) Abnormal glomerular filtration rate, renal plasma flow, and renal protein excretion in recent and short-term diabetics. Br Med J 2(5804):13–19PubMedPubMedCentralCrossRef
3.
Mogensen CE (1972) Kidney function and glomerular permeability to macromolecules in juvenile diabetes with special reference to early changes. Dan Med Bull 19(Suppl 3):1–40
4.
Jerums G, Premaratne E, Panagiotopoulos S, MacIsaac RJ (2010) The clinical significance of hyperfiltration in diabetes. Diabetologia 53(10):2093–2104PubMedCrossRef
5.
Tomaszewski M, Charchar FJ, Maric C, McClure J, Crawford L, Grzeszczak W et al (2007) Glomerular hyperfiltration: a new marker of metabolic risk. Kidney Int 71(8):816–821PubMedCrossRef
6.
7.
Park M, Yoon E, Lim YH, Kim H, Choi J, Yoon HJ (2015) Renal hyperfiltration as a novel marker of all-cause mortality. J Am Soc Nephrol JASN 26(6):1426–1433PubMedCrossRef
8.
Dupuis ME, Nadeau-Fredette AC, Madore F, Agharazii M, Goupil R (2020) Association of glomerular hyperfiltration and cardiovascular risk in middle-aged healthy individuals. JAMA Netw Open 3(4):e202377PubMedPubMedCentralCrossRef
9.
Kim Y, Lee S, Lee Y, Kang MW, Park S, Park S et al (2020) Glomerular hyperfiltration and cancer: a nationwide population-based study. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol 29(10):2070–2077CrossRef
10.
Kang MW, Park S, Lee S, Lee Y, Cho S, Han K et al (2020) Glomerular hyperfiltration is associated with dementia: a nationwide population-based study. PLoS ONE 15(1):e0228361PubMedPubMedCentralCrossRef
11.
Eriksen BO, Løchen ML, Arntzen KA, Bertelsen G, Eilertsen BAW, von Hanno T et al (2014) Subclinical cardiovascular disease is associated with a high glomerular filtration rate in the nondiabetic general population. Kidney Int 86(1):146–153PubMedCrossRef
12.
van der Sande NG, Blankestijn PJ, Leiner T, van der Graaf Y, de Borst GJ, Cramer MJ et al (2017) High ratios of kidney function to kidney size are related to mortality and kidney function decline in high-risk patients. Eur J Prev Cardiol 24(9):926–933PubMedCrossRef
13.
Penno G, Orsi E, Solini A, Bonora E, Fondelli C, Trevisan R et al (2020) Renal hyperfiltration is independently associated with increased all-cause mortality in individuals with type 2 diabetes: a prospective cohort study. BMJ Open Diabetes Res Care 8(1):e001481PubMedPubMedCentralCrossRef
14.
Melsom T, Schei J, Stefansson VTN, Solbu MD, Jenssen TG, Mathisen UD et al (2016) Prediabetes and risk of glomerular hyperfiltration and albuminuria in the general nondiabetic population: a prospective cohort study. Am J Kidney Dis 67(6):841–850PubMedCrossRef
15.
Low S, Zhang X, Wang J, Yeoh LY, Liu YL, Ang KKL et al (2018) Long-term prospective observation suggests that glomerular hyperfiltration is associated with rapid decline in renal filtration function: a multiethnic study. Diab Vasc Dis Res 15(5):417–423PubMedCrossRef
16.
Oh SW, Yang JH, Kim MG, Cho WY, Jo SK (2020) Renal hyperfiltration as a risk factor for chronic kidney disease: a health checkup cohort study. PLoS ONE 15(9):e0238177PubMedPubMedCentralCrossRef
17.
Xie Y, Bowe B, Mokdad AH, Xian H, Yan Y, Li T et al (2018) Analysis of the global burden of disease study highlights the global, regional, and national trends of chronic kidney disease epidemiology from 1990 to 2016. Kidney Int 94(3):567–581PubMedCrossRef
18.
Magee GM, Bilous RW, Cardwell CR, Hunter SJ, Kee F, Fogarty DG (2009) Is hyperfiltration associated with the future risk of developing diabetic nephropathy? A meta-analysis. Diabetologia 52(4):691–697PubMedCrossRef
19.
Murray CJL, Abbafati C, Abbas KM, Abbasi M, Abbasi-Kangevari M, Abd-Allah F et al (2020) Five insights from the global burden of disease study 2019. Lancet 396(10258):1135–1159CrossRef
20.
OuldSetti M, Kacimi SEO, Niskanen L, Tuomainen TP (2022) Mortality-based definition of renal hyperfiltration in middle-aged men: a 35-year cohort from Finland. Int Urol Nephrol 54(7):1673–1680CrossRef
21.
Daniel RM, De Stavola BL, Cousens SN (2011) Gformula: estimating causal effects in the presence of time-varying confounding or mediation using the G-computation formula. Stata J 11(4):479–517CrossRef
22.
Salonen JT (1988) Is there a continuing need for longitudinal epidemiologic research? The Kuopio ischaemic heart disease risk factor study. Ann Clin Res 20(1–2):46–50PubMed
23.
Ilomäki J, Hajat A, Kauhanen J, Kurl S, Kaufman JS, Tuomainen TP et al (2012) Relationship between alcohol consumption and myocardial infarction among ageing men using a marginal structural model. Eur J Public Health 22(6):825–830PubMedCrossRef
24.
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612PubMedPubMedCentralCrossRef
25.
Levey AS, Coresh J, Greene T, Marsh J, Stevens LA, Kusek JW et al (2007) Expressing the modification of diet in renal disease study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin Chem 53(4):766–772PubMedCrossRef
26.
Chagnac A, Weinstein T, Herman M, Hirsh J, Gafter U, Ori Y (2003) The effects of weight loss on renal function in patients with severe obesity. J Am Soc Nephrol 14(6):1480–1486PubMedCrossRef
27.
Palatini P (2012) Glomerular hyperfiltration: a marker of early renal damage in pre-diabetes and pre-hypertension. Nephrol Dial Transplant 27(5):1708–1714PubMedCrossRef
28.
Maeda I, Hayashi T, Sato KK, Koh H, Harita N, Nakamura Y et al (2011) Cigarette smoking and the association with glomerular hyperfiltration and proteinuria in healthy middle-aged men. Clin J Am Soc Nephrol 6(10):2462–2469PubMedPubMedCentralCrossRef
29.
Mickelsson M, Söderström E, Stefansson K, Andersson J, Söderberg S, Hultdin J (2021) Smoking tobacco is associated with renal hyperfiltration. Scand J Clin Lab Invest 81(8):622–628PubMedCrossRef
30.
Lin M, Su Q, Huang H, Zheng Y, Wen J, Yao J et al (2017) Alcohol consumption and the risk for renal hyperfiltration in the general Chinese population. Eur J Clin Nutr 71(4):500–505PubMedCrossRef
31.
Jhee JH, Nam KH, An SY, Cha MU, Lee M, Park S et al (2018) Severe vitamin D deficiency is a risk factor for renal hyperfiltration. Am J Clin Nutr 108(6):1342–1351PubMedCrossRef
32.
Nurmi T, Tuomainen TP, Virtanen J, Mursu J, Voutilainen S (2013) High-performance liquid chromatography and coulometric electrode array detector in serum 25-hydroxyvitamin D(3) and 25-hydroxyvitamin D(2) analyses. Anal Biochem 435(1):1–9PubMedCrossRef
33.
34.
Kanerva N, Kaartinen NE, Schwab U, Lahti-Koski M, Männistö S (2014) The Baltic Sea diet score: a tool for assessing healthy eating in Nordic countries. Public Health Nutr 17(8):1697–1705PubMedCrossRef
35.
Baron RM, Kenny DA (1986) The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. J Pers Soc Psychol 51(6):1173–1182PubMedCrossRef
36.
37.
VanderWeele TJ, Vansteelandt S, Robins JM (2014) Effect decomposition in the presence of an exposure-induced mediator-outcome confounder. Epidemiology 25(2):300–306PubMedPubMedCentralCrossRef
38.
Robins J (1986) A new approach to causal inference in mortality studies with a sustained exposure period—application to control of the healthy worker survivor effect. Math Model 7(9):1393–1512CrossRef
39.
Shi B, Choirat C, Coull BA, VanderWeele TJ, Valeri L (2021) CMAverse: A suite of functions for reproducible causal mediation analyses. Epidemiology 32(5):e20PubMedCrossRef
40.
41.
Pearl J, Glymour M, Jewell NP (2016) Causal Inference in Statistics: a Primer, 1st edn. Wiley, Chichester, p 160
42.
43.
44.
Rijnhart JJM, Lamp SJ, Valente MJ, MacKinnon DP, Twisk JWR, Heymans MW (2021) Mediation analysis methods used in observational research: a scoping review and recommendations. BMC Med Res Methodol 21(1):226PubMedPubMedCentralCrossRef
45.
Tonneijck L, Muskiet MHA, Smits MM, van Bommel EJ, Heerspink HJL, van Raalte DH et al (2017) Glomerular hyperfiltration in diabetes: mechanisms, clinical significance, and treatment. J Am Soc Nephrol 28(4):1023–1039PubMedPubMedCentralCrossRef
46.
Vallon V, Gerasimova M, Rose MA, Masuda T, Satriano J, Mayoux E et al (2014) SGLT2 inhibitor empagliflozin reduces renal growth and albuminuria in proportion to hyperglycemia and prevents glomerular hyperfiltration in diabetic Akita mice. Am J Physiol Renal Physiol 306:F194-204PubMedCrossRef
47.
Knight EL, Stampfer MJ, Hankinson SE, Spiegelman D, Curhan GC (2003) The impact of protein intake on renal function decline in women with normal renal function or mild renal insufficiency. Ann Intern Med 138(6):460–467PubMedCrossRef
48.
Yoo KD, Yoon HJ, Hwang SS, Heo NJ, Chin HJ, Yang SH et al (2017) Different association between renal hyperfiltration and mortality by sex. Nephrology 22(10):804–810PubMedCrossRef
49.
Gaspari F, Ruggenenti P, Porrini E, Motterlini N, Cannata A, Carrara F et al (2013) The GFR and GFR decline cannot be accurately estimated in type 2 diabetics. Kidney Int 84(1):164–173PubMedCrossRef
50.
Sundin PO, Udumyan R, Fall K, Montgomery S (2019) Grip strength modifies the association between estimated glomerular filtration rate and all-cause mortality. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc Eur Ren Assoc 34(10):1799–1801
51.
Stefansson VTN, Schei J, Jenssen TG, Melsom T, Eriksen BO (2016) Central obesity associates with renal hyperfiltration in the non-diabetic general population: a cross-sectional study. BMC Nephrol 17(1):172PubMedPubMedCentralCrossRef
Metadata
Title
The association between renal hyperfiltration and mortality is not mediated by diabetes mellitus
Authors
Mounir Ould Setti
Ari Voutilainen
Leo Niskanen
Tomi-Pekka Tuomainen
Publication date
23-03-2023
Publisher
Springer Netherlands
Keyword
Diabetes
Published in
International Urology and Nephrology / Issue 10/2023
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-023-03562-9

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