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Does type 2 diabetes mellitus delay renal failure in autosomal dominant polycystic kidney disease?
Rebecca Backenroth1, Mordecai M Popovtzer
1Nephrology and Hypertension Services, Hadassah University Hospital, Jerusalem, Israel. backenroth@hadassah.org.il
Insights
Individuals with autosomal dominant polycystic kidney disease (ADPKD) and type 2 diabetes experienced a significant delay in kidney failure onset. This suggests a potential protective effect of diabetes in ADPKD progression.
Area of Science:
- Nephrology
- Endocrinology
- Genetics
Background:
- Autosomal dominant polycystic kidney disease (ADPKD) is a prevalent genetic disorder leading to renal failure.
- Currently, no effective therapies exist to slow the progression of ADPKD.
- Disease onset and progression can vary, influenced by genetic and environmental factors.
Observation:
- Two ADPKD kindreds exhibited a notable delay in renal insufficiency onset among individuals with type 2 diabetes mellitus (T2DM).
- Nondiabetic ADPKD patients required dialysis or experienced renal death between ages 38-52.
- Diabetic ADPKD patients initiated dialysis or maintained renal function significantly later, around age 61.
Findings:
- The onset of end-stage renal disease in ADPKD was delayed by over 15 years in patients with T2DM.
- Diabetic patients developed T2DM around age 32 and were treated for approximately 19 years before insulin therapy.
- Cardiovascular disease was a prominent comorbidity in the diabetic ADPKD cohort.
Implications:
- Type 2 diabetes mellitus may confer a protective effect against accelerated renal failure in ADPKD.
- Potential mechanisms, such as glibenclamide's inhibition of the cystic fibrosis transmembrane conductance regulator, warrant further investigation.
- This observation highlights a critical area for future research into ADPKD therapeutic strategies.
Abstract:
Autosomal dominant polycystic kidney disease (ADPKD) is a common renal disease without an effective therapeutic intervention to delay renal failure. Within kindreds, renal dysfunction often develops at a similar age in affected individuals, although there are known modifying factors. Two kindreds with ADPKD have shown a striking pattern of delayed onset of renal insufficiency in those individuals also suffering from type 2 diabetes mellitus. Eight nondiabetic patients with ADPKD had onset of dialysis or renal death at ages 38-52 years, (mean +/- SEM 46 +/- 1.9, n = 7) as compared with four diabetics who started dialysis or are still off dialysis at the age of 61 +/- 2.8 years (p < 0.01). Two of the four diabetics still have reasonable renal function at age 61 and 66. The diabetes was diagnosed at age 32 +/- 2 years and was treated with oral hypoglycemics for 19 +/- 2 years before institution of insulin. Cardiovascular disease dominated the clinical picture in the diabetics. In conclusion, onset of renal failure in ADPKD was delayed for over 15 years in individuals who also suffered from type 2 diabetes mellitus, in two ADPKD kindreds. Possible mechanisms are discussed, including glibenclamide inhibition of the cystic fibrosis transmembrane conductance regulator. The striking delay associated with type 2 diabetes mellitus in ADPKD induced renal failure should be evaluated further.