Cardiac autonomic neuropathy predicts renal decline in type 1 diabetes mellitus: a 15 year follow-up study

Q: What are the key findings of this study?

Baseline cardiac autonomic neuropathy in patients with type 1 diabetes was independently associated with a 3.5-fold higher odds of a composite renal outcome over 15 years compared to no CAN.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Type 1 diabetes mellitus (n=87). Intervention: Cardiac autonomic neuropathy (CAN) vs. No cardiac autonomic neuropathy. Primary outcome: Composite renal outcome (severely increased albuminuria, progression to higher KDIGO risk category, ≥30% decline in eGFR, or initiation of kidney replacement therapy) (OR 3.5, 95% CI 1.1-10.7, p=0.03).

Q: What does this research mean for the field?

Cardiac autonomic neuropathy independently predicts accelerated eGFR decline and increased albuminuria over 15 years in individuals with type 1 diabetes. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Kywe Kywe Soe; Emma Robinson; Misbah Oleolo; Mohummad Shaan Goonoo; Gordon Sloan; Simon Heller; Solomon Tesfaye; Jefferson Luiz Brum Marques; Steven Sourbron; Dinesh Selvarajah

doi:10.1007/s00125-026-06818-y

July 29, 2026DiabetologiaOpen Access

Cardiac autonomic neuropathy predicts renal decline in type 1 diabetes mellitus: a 15 year follow-up study

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Key result

Baseline cardiac autonomic neuropathy is linked to ~3.5-fold higher odds of renal outcomes in T1D.

OR 3.5
95% CI 1.1-10.7
P=0.03
n=87

Figures

Why the study?

It was unknown whether cardiac autonomic neuropathy is an independent risk factor for kidney function decline in type 1 diabetes mellitus over a 15-year follow-up period.

Does cardiac autonomic neuropathy predict accelerated renal function decline and increased albuminuria in patients with type 1 diabetes?

Key Points

To determine whether cardiac autonomic neuropathy independently predicts kidney function decline and albuminuria progression in type 1 diabetes over a 15-year follow-up period.
Enrolled 87 participants with type 1 diabetes and baseline eGFR >30 ml/min per 1.73 m2 who underwent cardiovascular autonomic reflex testing.
Retrieved renal data (eGFR and UACR) at 4-year intervals over 15 years and evaluated longitudinal trajectories using linear mixed-effects models adjusted for potential confounders.
Participants with established CAN showed a mean (SD) eGFR decline of 14.8 (21.6) ml/min per 1.73 m2 compared with 3.1 (7.3) in early CAN and 3.3 (7.4) without CAN (p=0.004).
In fully adjusted mixed-effects models, baseline CAN independently predicted faster eGFR decline (-0.66 vs -0.30 ml/min per 1.73 m2 per year; p=0.018) and greater longitudinal increases in UACR (p=0.002).
The composite renal outcome occurred in 30.6% (n=11) of participants with CAN versus 11.8% (n=6) without CAN, conferring 3.5-fold higher odds (OR 3.5 [95% CI 1.1, 10.7]; p=0.03).

Study Design

Type

Cohort (n=87)

Multicenter

No

Structured PICO

Does cardiac autonomic neuropathy predict accelerated renal function decline and increased albuminuria in patients with type 1 diabetes?

P

Population

87 adults aged 18-75 years with type 1 diabetes and preserved renal function at baseline, followed for 15 years to assess the impact of cardiac autonomic neuropathy on kidney function.

E

Exposure

Presence of Cardiac Autonomic Neuropathy (CAN) at baseline (early or established), assessed by cardiovascular autonomic reflex tests.

C

Comparator

Absence of Cardiac Autonomic Neuropathy (No CAN) at baseline.

O

Outcome

Longitudinal changes in eGFR and UACR, and a composite kidney outcome (first occurrence of severely increased albuminuria >30 mg/mmol, progression to a higher KDIGO risk category, sustained ≥30% decline in eGFR, or initiation of kidney replacement therapy) over 15 years.composite

Main Result

Odds Ratio: 3.5 (95% CI 1.1–10.7)

Absolute Event Rate: 30.6% vs 11.8%

p-value: p=0.03

Cardiac autonomic neuropathy is an independent predictor of accelerated eGFR decline and increased albuminuria in patients with type 1 diabetes over a 15-year period.

Limitations

Small sample size limiting subgroup analyses
Exclusion of mortality from the composite renal endpoint, potentially introducing survivorship bias
Potential influence of medications on cardiovascular autonomic reflex test findings
Individual CART components were not available for separate analysis
Blood samples were collected at 4-year intervals rather than annually
Small number of participants with advanced DKD at baseline
Outcome data beyond death were unavailable
Data on race/ethnicity were not collected

Implication

May support CAN screening for renal risk in T1D; hypothesis-generating and requires larger prospective validation.

Abstract

Aims/hypothesis The aim of this study was to determine whether cardiac autonomic neuropathy (CAN) is an independent risk factor for kidney function decline in type 1 diabetes mellitus over a 15 year follow-up period. Methods Eighty seven participants with type 1 diabetes and eGFR >30 ml/min per 1.73 m 2 underwent cardiovascular autonomic reflex testing at baseline. Renal data were retrieved at 4 year intervals over 15 years. Stratification of participants into Kidney Disease: Improving Global Outcomes (KDIGO) chronic kidney disease progression prognostic risk was done by using eGFR and urinary albumin/creatinine ratio (UACR). Longitudinal changes in eGFR and UACR were analysed using linear mixed-effects models with adjustment for potential confounders to determine whether CAN is an independent predictor of eGFR and UACR change over 15 years. Results At baseline, higher KDIGO risk category was associated with increased severity of CAN ( r =0.38, p <0.001) and increase in UACR ( p <0.001) compared with the lower risk group. Participants with established CAN at baseline exhibited greater mean (SD) eGFR decline of 14.8 (21.6) ml/min per 1.73 m 2 , compared with 3.1 (7.3) and 3.3 (7.4) ml/min per 1.73 m 2 in the early stage and those without CAN ( p =0.004). Mean (SD) increases in UACR were 0.4 (0.9), 11.3 (30.4) and 4 (8.9) mg/mmol for no CAN, early CAN and established CAN ( p =0.03), respectively. After adjusting for potential confounders, baseline CAN was independently associated with both accelerated eGFR decline ( p =0.018) and greater increases in UACR ( p =0.002) over time. Conclusions/interpretation CAN is an independent predictor of both accelerated eGFR decline and increased albuminuria in type 1 diabetes. The study also explored the relationship between CAN and KDIGO prognostic risk in diabetic kidney disease, demonstrating that increased severity of CAN is associated with higher KDIGO prognostic risk.

Discussion

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Cite This Study

Soe et al. (2026) conducted a cohort in Type 1 diabetes mellitus (n=87). Cardiac autonomic neuropathy (CAN) vs. No cardiac autonomic neuropathy was evaluated on Composite renal outcome (severely increased albuminuria, progression to higher KDIGO risk category, ≥30% decline in eGFR, or initiation of kidney replacement therapy) (OR 3.5, 95% CI 1.1-10.7, p=0.03). Baseline cardiac autonomic neuropathy in patients with type 1 diabetes was independently associated with a 3.5-fold higher odds of a composite renal outcome over 15 years compared to no CAN.

synapsesocial.com/papers/6a6c4755747664a1aa73c7ed https://doi.org/10.1007/s00125-026-06818-y

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Cardiac autonomic neuropathy predicts renal decline in type 1 diabetes mellitus: a 15 year follow-up study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Cardiac autonomic neuropathy predicts renal decline in type 1 diabetes mellitus: a 15 year follow-up study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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