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Pathway to CKD

Apr 22, 2017

Study looks at the heterogeneity of CKD in type 1 diabetes.

According to the National Kidney Foundation, approximately 30% of type 1 diabetes patients will eventually suffer from kidney failure. It is well known that diabetes can cause damage to the small blood vessels in the kidneys, making them less efficient at clearing water and salt from the blood, with the early markers of chronic kidney disease being albuminuria followed by GFR loss. Currently, urinary albumin excretion is routinely measured during screening for chronic kidney disease, but researchers have recently found this screening may not be true for everyone. The UK Prospective Diabetes Study (UKPDS) found that about 50% of type 2 diabetes patients who developed renal impairment had no prior albuminuria. Another survey, the National Health and Nutrition Examination (NHANES), shows there may be a trend in CKD phenotype changes, suggested by the rate of CKD in diabetes patients staying the same, but the albumin-to-creatinine ratio (ACR) trending down while the prevalence of eGFR <60ml min-1 has increased.

The study was a retrospective, single-center analysis of patients with type 1 diabetes to determine the prevalence of CKD phenotypes, describe associations with other diabetes complications, and identify any differences in the associated factors. Inclusion criteria was comprised of the diagnosis of type 1 diabetes before the age of 36 requiring immediate insulin use and continued use one year after diagnosis and the eligible individuals attending a screening for complications at the institution. Exclusion criteria included diabetes diagnosis of less than one year, pregnancy, non-white ethnicity, and dialysis or renal transplant.  At least three samples of first-void urine collected at 1-month intervals was used to determine ACR. Measurements of eGFR, CKD stage, and HbA1c, and BMI, and cholesterol were also collected for each participant.

A total of 777 type 1 diabetes patients was analyzed in the final study. The majority of the study participants had normal albuminuria (91.6%), while 6.4% of patients had microalbuminuria (ACR 3.4-34 mg/mmol) and 1.9% had macroalbuminuria (ACR > 34 mg/mmol). Those considered albuminuric typically were hypertensive, on BP-lowering agents and antiplatelet agents, and had higher daily insulin requirements. Compared to patients with normal albuminuria, those with increased albuminuria were more likely to have a higher HbA1c, fibrinogen, higher rates of hypertension, and larger occurrence of advanced retinopathy. The majority of patients in the study had no CKD, while 6.8% were classified as stage 1-2 and 3.7% were stage 3 or higher. For eGFR measurements, 57.3% of patients were category 1 (eGFR>90), 39.0% were category 2, (eGFR 60-89), and 3.7% were category 3 (eGFR <60) with age, diabetes duration, and BMI increasing across the categories. The participants with CKD >3 were separately analyzed for albuminuric and non-albuminuric phenotypes. The only significant differences between the group were lower eGFR (45.2 ± 10.8 vs 52.2 ± 7.4 ml min−1 [1.73 m]−2, p = 0.048) in the Alb+ group and a trend towards significance of higher HbA1c (8.62 ± 1.33 vs 7.84 ± 1.13% [70.8 ± 14.6 vs 62.2 ± 12.4 mmol/mol]; p = 0.080). Patients with CKD and ALB+ phenotype correlated with a longer duration of diabetes, HbA1c, and hypertension, in contrast CKD ALB- phenotype patients correlated with just age and hypertension.  A similar analysis was performed using individuals with an eGFR <75, with 11.3% of patients having Alb+ phenotype and 88.7% having Alb- phenotype. Pooling eGFR and stage 3 CKD data revealed that patients who were Alb+ phenotype had higher BMI, HbA1c, and fibrinogen, larger waist circumference, and lower HDL.

This study found that CKD in type 1 diabetes patients may be more heterogenic than originally thought. While the majority of patients were Alb+ phenotype, a large percent of patients with CKD stage 3 or worse were Alb- phenotype. Limitations of this study include the completely white ethnic population and a single estimate of eGFR used restricting tracking of changes over time.

Practice Pearls:

  • Both Alb+ and Alb- phenotypes are present in CKD patients with type 1 diabetes.
  • Fibrinogen levels may be an additional beneficial marker of CKD.
  • Further research is needed to determine if the Alb+ and Alb- phenotypes respond differently to therapy.



“Diabetes – A Major Risk Factor for Kidney Disease.” The National Kidney Foundation. N.p., 03 Feb. 2017. Web.

Penno, Giuseppe, Eleonora Russo, Monia Garofolo, Giuseppe Daniele, Daniela Lucchesi, Laura Giusti, Veronica Sancho Bornez, Cristina Bianchi, Angela Dardano, Roberto Miccoli, and Stefano Del Prato. “Evidence for two distinct phenotypes of chronic kidney disease in individuals with type 1 diabetes mellitus.” Diabetologia (2017). Web.

Priscilla Rettman, BS, PharmD Candidate 2017, Philadelphia College of Osteopathic Medicine- GA Campus