Clinical predictors differentiating non-diabetic renal diseases from diabetic nephropathy in a large population of type 2 diabetes patients
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)
- et al.
Renal outcomes in patients with type 2 diabetes with or without coexisting non-diabetic renal disease
Diabetes Res Clin Pract
(2011) - et al.
Non-diabetic renal diseases in diabetics
Clin Queries: Nephrol
(2012) - et al.
Prevalence and causes of albuminuria in non-insulin-dependent diabetic patients
Kidney Int
(1992) - et al.
Should there be an expanded role for kidney biopsy in the management of patients with type I diabetes?
Am J Kidney Dis
(1990) - et al.
Is there a need for changes in renal biopsy criteria in proteinuria in type 2 diabetes?
Diabetes Res Clin Pract
(2002) - et al.
Non-diabetic renal disease in Croatian patients with type 2 diabetes mellitus
Diabetes Res Clin Pract
(2014) - et al.
Detection of glomerular bleeding by phase-contrast microscopy
Lancet
(1982) - et al.
Clinical features of non-diabetic renal diseases in patients with type 2 diabetes
Diabetes Res Clin Pract
(2005) - et al.
Prevalence of non-diabetic renal disease in patients with type 2 diabetes
Diabetes Res Clin Pract
(2010) - et al.
Evaluation of renal biopsies in type 2 diabetic patients with kidney disease: a clinicopathological study of 216 cases
Int Urol Nephrol
(2013)
The modern spectrum of renal biopsy findings in patients with diabetes
Clin J Am Soc Nephrol
Prevalence of microalbuminuria, arterial hypertension, retinopathy and neuropathy in patients with insulin dependent diabetes
Br Med J (Clin Res Ed)
Increased prevalence of non-diabetic renal pathology in type II diabetes mellitus
Nephrol Dial Transplant
Clinical predictors of non-diabetic renal disease in patients with non-insulin dependent diabetes mellitus
Nephrol Dial Transplant
Identification of non-diabetic glomerular disease in renal biopsies from diabetics–a dilemma
Nephrol Dial Transplant
Clinical indicators which necessitate renal biopsy in type 2 diabetes mellitus patients with renal disease
Int J Clin Pract
Dysmorphic erythrocytes are superior to hematuria for indicating non-diabetic renal disease in type 2 diabetics
J Diabetes Investig
Cited by (54)
Glomerular Hematuria and the Utility of Urine Microscopy: A Review
2022, American Journal of Kidney DiseasesParallelism and non-parallelism in diabetic nephropathy and diabetic retinopathy
2024, Frontiers in EndocrinologyPresence of Non-Diabetic Kidney Diseases in Biopsy Specimens of Diabetic Patients’ Single Center Experience
2023, International Journal of Molecular SciencesAnalysis of clinical predictors of kidney diseases in type 2 diabetes patients based on machine learning
2023, International Urology and Nephrology