Clinical predictors differentiating non-diabetic renal diseases from diabetic nephropathy in a large population of type 2 diabetes patients

https://doi.org/10.1016/j.diabres.2016.09.005Get rights and content

Highlights

  • This study included a large sample of type 2 DM patients who underwent renal biopsy.

  • We included only patients with either DN or a NDRD to decrease confounding factors.

  • Clinical characteristics of NDRD patients was evaluated objectively.

  • Absence of retinopathy achieved the overall highest diagnostic efficiency.

Abstract

Aims

Non-diabetic renal diseases (NDRDs) are associated with better renal outcomes than diabetic nephropathy (DN). This study was conducted to determine the common clinical markers predicting NDRDs in type 2 diabetes patients.

Methods

Patients with type 2 diabetes mellitus who underwent a renal biopsy were screened. Eligible patients were categorized into two groups: DN group and NDRD group. Patient’s clinical characteristics and laboratory data were collected. Logistic regression analysis was performed to identify risk factors for NDRD development, and the diagnostic performance of these variables was evaluated.

Results

The study included 248 patients, 96 (38.71%) in the DN group and 152 (61.29%) in the NDRD group. Patients in the NDRD group had a shorter duration of DM and higher hemoglobin, estimated glomerular filtration rate, and urine osmotic pressure values as well as a higher incidence of glomerular hematuria than patients in the DN group. In the NDRD patients, the most common pathological type was membranous nephropathy (55, 36.18%). Absence of retinopathy (OR, 44.696, 95% CI, 15.91–125.566), glomerular hematuria (OR, 9.587, 95% CI, 2.027–45.333), and DM history ⩽5 years (OR, 4.636, 95% CI, 1.721–12.486) were significant and independent risk factors for the development of NDRD (P < 0.01). Absence of retinopathy achieved the overall highest diagnostic efficiency with a sensitivity of 92.11% and specificity of 82.29%. Glomerular hematuria had the highest specificity (93.75%).

Conclusion

Shorter duration of diabetes (⩽5 years), absence of retinopathy, and presence of glomerular hematuria were independent indicators associated with NDRDs, indicating the need for renal biopsy.

Introduction

Non-diabetic renal diseases (NDRDs) are currently recognized as a common complicating condition in type 2 diabetes patients and require accurate differential diagnosis and treatment from diabetic nephropathy (DN). It is generally accepted that NDRDs have a relatively better prognosis, because renal lesions in DN are deemed difficult to reverse. In contrast, NDRDs are often treatable and even remittable [1]. In practice, a large proportion of patients with type 2 diabetes mellitus (DM) are not formally evaluated with a renal biopsy [2], [3]. Instead of pathological diagnosis, DN is usually diagnosed based on clinical symptoms, and NDRD patients are potentially misdiagnosed with DN [4] and thus do not receive proper treatment.

Because NDRDs are associated with significantly better renal outcomes compared with biopsy-proven DN, it is important to identify diabetes patients who are likely to develop NDRDs. Different predicting factors have been identified for NDRDs, such as short duration of DM [5], absence of diabetic neuropathy or retinopathy, and microscopic hematuria [6], but these markers were found to have variable predictive values in different studies. In fact, most knowledge regarding the nature of kidney diseases in type 2 DM patients is derived from studies of patients with type 1 DM. However, patients with type 1 DM show less heterogeneity than their counterparts with type 2 DM, and only 5% of type 1 DM patients have NDRDs [4], [7]. Thus, patients are easily diagnosed with type 1 DM if the patient has a relatively longer history of DM or presents with diabetic retinopathy, which corresponds to a rate of pathological diagnosis of 95% [8], [9]. On the contrary, NDRDs represent a rare clinical condition in type 1 DM, particularly in patients with a DM history of 10 years, with a rate of 2–3% [10]. In comparison to those in type 1 DM patients, the renal diseases in type 2 DM patients are more complex and heterogeneous, creating difficulties in the differential diagnosis of NDRDs from DN. Also, the occurrence of NDRDs is more common in type 2 DM patients, although different incidences have been reported in different regions [4], [7]. Some prospective studies have suggested that biopsy criteria for type 1 DM are not useful for identifying type 2 DM patients with other potentially treatable renal diseases like NDRDs [11]. The present study was conducted to determine the frequency of NDRDs in type 2 DM patients in China and also to identify common clinical markers associated with NDRDs in the type 2 diabetic population. Previous studies usually included patients with coexisting DN and NDRDs [12], [13], probably due to limited sample sizes, but this increases systematic errors due to confounding factors. In the present study, we included only patients with either DN or a NDRD in order to evaluate the diagnostic performance of clinical markers for predicting NDRD development in type 2 DM patients.

Section snippets

Study population

A total of 384 patients with type 2 DM who underwent a renal biopsy between April 2012 and December 2014 in our hospital were screened. The inclusion criteria were: (1) male or female, age  18 years; (2) biopsy-proven renal lesion; and (3) proteinuria (>0.15 g/24 h). The exclusion criteria were: (1) incomplete data or unclear medical history; (2) lack of a fundus examination; (3) complications, such as severe infection (urinary tract, respiratory tract, digestive tract, etc.) and/or malignancy; (4)

Clinical characteristics and laboratory data of patients

The final study population included 248 patients (173 men, 69.76%), with 96 (38.71%) in the DN group and 152 (61.29%) in the NDRD group. The mean age of the patients was 50.23 ± 10.25 years (range, 26–73 years) at the time of renal biopsy. The patients in the DN group were more likely to have a family history of DM, hypertension, and diabetic retinopathy, compared with those in the NDRD group (P < 0.01). In addition, a greater percentage of patients in the NDRD group (63.6%) had a short history of DM

Discussion

The prevalence of NDRDs in type 2 DM patients varies widely in different regions, ranging from 27% to 93.5% [2], [18], depending on the selection criteria, threshold of biopsy, and population studied. A novel strength of the present study was the lack of restrictions on age and creatinine value in patient enrollment and also the inclusion of those with suspected DN in order to minimize selection bias as much as possible. The results showed that the NDRD incidence was 61.29% among 248 type 2 DM

Conflicts of interest

None.

Acknowledgements

This study was partially supported by the National Basic Research program of China (973 Program; No. 2013CB530803, 2015CB553605), grants from the Science and Technology Project of Beijing (Nos. D13110700470000, D131100004713003), and grants from Chinese PLA General Hospital (Nos. 2016FC-TSYS-1043, 16KMM08). We thank Medjaden Bioscience Limited for editing and proofreading the manuscript.

References (35)

  • S.G. Sharma et al.

    The modern spectrum of renal biopsy findings in patients with diabetes

    Clin J Am Soc Nephrol

    (2013)
  • H.H. Parving et al.

    Prevalence of microalbuminuria, arterial hypertension, retinopathy and neuropathy in patients with insulin dependent diabetes

    Br Med J (Clin Res Ed)

    (1988)
  • D. Kleinknecht et al.

    Increased prevalence of non-diabetic renal pathology in type II diabetes mellitus

    Nephrol Dial Transplant

    (1992)
  • S.K. Mak et al.

    Clinical predictors of non-diabetic renal disease in patients with non-insulin dependent diabetes mellitus

    Nephrol Dial Transplant

    (1997)
  • S. Olsen

    Identification of non-diabetic glomerular disease in renal biopsies from diabetics–a dilemma

    Nephrol Dial Transplant

    (1999)
  • Y.L. Lin et al.

    Clinical indicators which necessitate renal biopsy in type 2 diabetes mellitus patients with renal disease

    Int J Clin Pract

    (2009)
  • Z.Y. Dong et al.

    Dysmorphic erythrocytes are superior to hematuria for indicating non-diabetic renal disease in type 2 diabetics

    J Diabetes Investig

    (2016)
  • Cited by (54)

    View all citing articles on Scopus
    View full text