A recent study confirms the link between early diabetic neuropathy and incipient kidney damage in well-controlled patients with type 2 diabetes. However, scientists point out that this connection was demonstrated over 30 years ago – and largely forgotten. An article in Frontiers in Clinical Diabetes and Healthcare recalls the pioneering work of Swedish researcher Göran Sundkvist.
Background
In diabetes mellitus, neuropathy and nephropathy are among the classic microvascular complications. Both are associated with an unfavorable prognosis. While diabetic neuropathy often occurs early, nephropathy is considered one of the most serious consequences of the disease. A recent cross-sectional study by Zaki et al. (2025) showed a significant association between clinical peripheral neuropathy and elevated urinary albumin-to-creatinine ratio in patients with well-controlled type 2 diabetes and preserved kidney function.
The forgotten pioneering work
As early as 1993, Swedish researcher Göran Sundkvist published a prospective study in which he demonstrated that cardiac autonomic neuropathy (CAN) predicts a decline in glomerular filtration rate in patients with type 1 diabetes. Patients with CAN showed a fourfold greater decline in kidney function over 10–11 years compared to patients without autonomic neuropathy. Sundkvist presented these findings at a Neurodiab meeting in 1992, where they were initially met with criticism.
Since this initial work, 16 out of 18 long-term studies have confirmed that measures of autonomic neuropathy are independent predictors of the progression of diabetic nephropathy.
Possible mechanisms
The authors of the current article discuss several mechanisms by which autonomic neuropathy can promote kidney damage. These include disturbed circadian rhythm of sympathovagal balance with nocturnal blood pressure increase (reverse dipping), impaired neural regulation of renal blood flow, and CAN-associated inflammatory response. Recent research also views the kidney as an interoceptive organ that can influence systemic sympathetic activity itself via afferent nerves.
Implications for Clinical Practice
The authors emphasize that the early detection of neuropathy – especially the autonomic form – could help to identify patients at increased risk for progressive kidney disease earlier. At the same time, they recall that many of the connections discussed today were already described in the 1990s but received too little attention for a long time.
Professor Göran Sundkvist, who passed away in 2006, is considered one of the pioneers of diabetic neuropathy research. In his honor, the Young Investigators Award for Clinical Science of Neurodiab has been named after him since 2007.
Outlook
The authors see autonomic neuropathy as a potentially modifiable risk factor for the progression of diabetic nephropathy. Further studies are needed to clarify the extent to which early intervention in autonomic dysfunction can favorably influence the course of kidney disease.
FAQ
What does the current study by Zaki et al. show?
A link between early peripheral neuropathy and the onset of albuminuria in well-controlled type 2 diabetes.
Why is the work of Sundkvist referenced?
Because as early as 1993, Sundkvist demonstrated in a long-term study that autonomic neuropathy predicts a deterioration in kidney function – a connection that went largely unnoticed for a long time.
What mechanisms are discussed?
Impaired blood pressure regulation (reverse dipping), inflammatory processes, and impaired neural control of renal blood flow.
Does neuropathy have a causal impact on kidney damage?
There is strong evidence of a link, but the exact causal mechanisms are not yet fully understood.
What is the clinical relevance of the topic today?
Early detection of autonomic neuropathy could help to better identify patients at risk for progressive diabetic nephropathy.
