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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
ORIGINAL ARTICLE  
Year : 2017  |  Volume : 28  |  Issue : 2  |  Page : 307-312
Clinical variables differentiating diabetic from nondiabetic kidney disease in patients with diabetes: A single-center study


1 Department of Nephrology, Dorab Patel Post Graduate Training and Research Center, The Kidney Center Post Graduate Training Institute, Karachi, Pakistan
2 Department of Biostatistics and Research, Dow University of Health Sciences, Karachi, Pakistan

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Date of Web Publication23-Mar-2017
 

   Abstract 

Patients with diabetes may have kidney diseases other than the diabetic kidney disease. Kidney biopsy is the investigation of choice when this is suspected. This retrospective analysis included all patients known to have diabetes mellitus (DM) and who had a kidney biopsy at our center between 1998 and 2014. The aim of this study was to assess if an association exists between the clinical factors on the presence or absence of diabetic nephropathy (DNP). A total number of 206 patients were included in our study. The association between the diabetic retinopathy (DRP) and DNP was high (P = 0.001). We found that the DRP is highly specific for the presence of DNP [89.7% (78 out of 87)] whereas sensitivity of DRP for DNP was 56.3% (67 out of 119). Among other factors, only duration of DM showed a significant association (P = 0.005) (odds ratio: 1.1085 and confidence interval: 1.025–1.149) with the development of DNP. We conclude that the absence of DRP is strongly associated with the presence of nondiabetic renal disease while the presence of DRP has a low sensitivity for the presence of DNP.

How to cite this article:
Imtiaz S, Salman B, Nasir K, Drohlia MF, Ahmad A. Clinical variables differentiating diabetic from nondiabetic kidney disease in patients with diabetes: A single-center study. Saudi J Kidney Dis Transpl 2017;28:307-12

How to cite this URL:
Imtiaz S, Salman B, Nasir K, Drohlia MF, Ahmad A. Clinical variables differentiating diabetic from nondiabetic kidney disease in patients with diabetes: A single-center study. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2019 Jun 24];28:307-12. Available from: http://www.sjkdt.org/text.asp?2017/28/2/307/202794

   Introduction Top


The incidence of type II diabetes mellitus (DM) is increasing all over the world, especially in developing countries.[1] Diabetes in Asian countries, especially India, Bangladesh, and Pakistan is associated with rapid progression and with more severe complications.[2] It is predicted that by 2030, there will be 69% increase in the number of adults with DM in the developing countries compared to 20% increase in developed countries. According to the Pakistan National Diabetic Survey, the prevalence of DM in the urban versus rural areas was 6.0% in men and 3.5% in women against 6.9% in men and 2.5% in women, respectively.[3]

Diagnosis of diabetic retinopathy (DRP) is a simple bedside procedure while the definitive diagnosis of diabetic nephropathy (DNP) requires a kidney biopsy. Some found authors reported a strong association between DRP and DNP,[4],[5],[6],[7],[8] whereas others reported poor correlation.[9] If a strong relationship exists between DNP and DRP, this would be useful to differentiate nondiabetic proteinuric kidney diseases from diabetic disease and will also direct the nephrologist to select the patients for kidney biopsy.

The aim of this study is to evaluate the association between DRP, degree of proteinuria, hematuria, and hypertension on the presence or absence of DNP.


   Materials and Methods Top


This retrospective analysis included all patients who were known to have DM and had kidney biopsies at the Kidney Centre Post Graduate Training Institute during 1998–2014. The data were collected from the patients’ records. We included all patients with diabetes of more than 18 years of age who had complete records of eye examination and kidney biopsy. Kidney biopsies were performed in all patients who had a short history of diabetes and presented with proteinuria and having no retinopathy, those with hematuria or rapidly rising serum creatinine even in the presence of retinopathy. We defined DRP as background or proliferative on the basis of fundoscopic examination done by an ophthalmologist.

DNP was diagnosed by the presence of classical diabetic Kimmelstiel–Wilson nodular lesion or by the presence of mesangial expansion, diffuses intercapillary glomerulosclerosis, fibrin caps, capsular drops, and basement membrane thickening. Nondiabetic kidney diseases (NDKDs) were classified according to their established histopathological criteria. Duration of DNP was defined as the period between the onset of DM and kidney biopsy.

The clinical variables which were recorded at the time of kidney biopsy were age, gender, duration of DM, blood pressure, serum creatinine, serum albumin, hematuria, and urinary protein creatinine ratio.


   Statistical Analysis Top


Data were analyzed using Statistical Package for the Social Science (SPSS) software version 17.0 (SPSS Inc., Chicago, IL, USA). Mean ± standard deviation was computed for quantitative variable. Categorical variables were described in terms of frequencies and percentages. Chi-square test was performed to see the association between DNP and DRP. At univariable stage variables with P value at most 0.20 were included in multivariable analyses. Predicted model using logistic regression analysis was established to evaluate the effect of DRP on DNP. Validity of the model was assessed by receiver operating characteristic (ROC) curve, and decision was made on the basis of the area under the curve (AUC) value. Level of significance considered at 5%.


   Results Top


A total of 206 patients were included in our study. Their demographical and clinical parameters are shown in [Table 1] and [Table 2]. There were 124 (60.20%) males and 82 (39.80%) females. The mean age was 52.3 ± 11.9 years. The duration of DM, blood pressure, serum creatinine, serum albumin, and protein-creatinine ratio is shown in [Table 1]. There were 74 (35.9%) patients with DNP, 87 (42.2%) patients with NDKD, and 45 (22.8%) NDKD superimposed on DNP. Patients who had no evidence of DRP were 130 (63.1%), whereas those who had DRP were 76 (36.9%). DRP was background retinopathy in 46 (22.3%) patients and proliferative DRP in 30 (14.6%) patients [Table 2]. Among the DNP patients, 68 (33%) had mesangial expansion, whereas 20 (9.71%) had nodular sclerosis and 31 (15%) had advanced diabetic glomerulosclerosis [Table 2].
Table 1: Clinical and laboratory parameters of diabetic patients.

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Table 2: Clinical and histological status of patients.

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The association between the DRP and DNP was evaluated by Chi-square test, and the result showed a high association between these two variables (P = 0.00001) [Table 3]. Eighty-seven out of 206 (42.2%) had NDKD in whom DRP was also absent in 78 (89.7%). Conversely, of the patients who had DRP [119 out of 206 (57.8%)] patients had 67 (56.3%) had DRP.
Table 3: Association of diabetic retinopathy and diabetic nephropathy.

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Thus, the DRP is highly specific for the presence of DNP and the specificity of DRP for DNP is 89.7% (78 out of 87), whereas sensitivity of DRP for DNP is 56.3% (67 out of 119) [Table 3].

To evaluate the effect of different variables on DNP, univariable logistic regression was done and revealed that DRP and duration of DM had a very significant effect (P <0.001 and P = 0.005, respectively). Odds ratio of background retinopathy for the presence of DNP was 15.75 times, whereas proliferative retinopathy was 7.5 times as compared to no retinopathy. The chances of DNP increased up to 1.08 times with ear year increase in the duration of DM [Table 4]. When these variables along with serum creatinine and albumin were assessed in multivariable logistic regression model, the duration of DM became insignificant (P = 0.27), whereas serum creatinine became significant (P = 0.042). For each 1 mg/ dL increased in serum creatinine, the chances of DNP decreased by 9%. On the other hand, retinopathy remained highly significantly associated with the presence of DNP [Table 4].
Table 4: Adjusted and unadjusted odds ratio of variables for the presence of diabetic nephropathy.

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The accuracy of the predicted model was checked by the ROC curve which showed that the AUC was 0.791. Therefore, the model is 79.1% accurate for the prediction, and ROC curve is highly significant (P = 0.0001 with 95% confidence interval: 0.650-0.792) [Figure 1].
Figure 1: Area under curve is 0.79.

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   Discussion Top


The relationship between DNP and DRPC is more predictable in type I diabetics. Patients with one microvascular complication almost always have other signs of diabetic microvascular disease.[10],[11],[12],[13]

In case of type II DM, this relationship is less predictable, and there is relatively high prevalence of NDKD in this group of patients. This is the reason several authors recommended routine kidney biopsy in type II patients.[14] The decision to do a renal biopsy should be made after evaluating every individual case and on the basis of clinical and laboratory parameter. Such evaluation would include the presence or absence of DRP, hematuria, progression of kidney disease, and duration of DM.

Among the various factors which could help to differentiate clinically between diabetic and NDKD such as age, gender diabetic duration, blood pressure, serum albumin, serum creatinine, hematuria, and degree of proteinuria, we found that a short duration of DM and absence of DRP strongly suggest the presence of NDKD. This is consistent with many studies[11],[12],[13],[14],[15] and two meta-analyses,[6],[8] while some of the investigators found a weak correlation with these two variables.[16],[17],[18]

We found a specificity of DRP for the absence of DNP of 89% and a sensitivity of DRP for the presence of DNP of 56%. This suggested that the DRP occurred significantly less frequently in patients with type II diabetes who had NDKD when compared to patients with DNP. Chong and Keng[16] in a retrospective analysis of 110 patients examined the presence of nondiabetic renal disease (NDRD) in patients with type II diabetes and evaluated the clinical markers for DNP. They found the presence of DRP is strongly associated with DNP. In their study, DRP was found in 84% (61/73) of the patients with DNP, and 91% (61/67) of patients with DRP had DNP. They concluded that the presence of DRP can predict the presence of DNP with a sensitivity of 84% and specificity of 63%. In another study, Zhou and Chen developed a diagnostic model which can predict the underlying cause of proteinuria in patients with diabetes. They found that 90% of their patients with type II diabetes with retinopathy had DNP and 76% of patients with diabetes without DRP had NDRD in their biopsy. They concluded that the absence of DRP is a good indicator for NDRD.[17]

Contrary to most of the papers, which showed a strong correlation between retinopathy and nephropathy, some of the investigators found a poor relationship between the two. Mak et al[18] in a prospective cohort of 51 patients with proteinuria studied the prevalence of NDRD among a Chinese population with type II diabetes. They found that the presence of hematuria and nonnephrotic proteinuria to be predictors of NDRD, whereas the absence of DRP and neuropathy was poor predictors of NDRD. In another prospective study, Prakash et al[9] followed 23 patients with type II diabetes and found that the presence or absence of DRP does not differentiate between diabetic and NDKD. Likewise, Kanauchi et al[19] described five patients who had no evidence of retinopathy and had DNP in kidney biopsy. All of these studies have a problem with their small size.

We also found that the duration of DM has a significant effect on the presence or absence of DNP. Chong and Keng in a retrospective analysis of type II DM patients also found a correlation of duration and DNP. They speculate that a duration of more than 10 years predicts the possibility of DNP.[16] Liang et al in a meta-analysis of 26 studies concluded that the duration of DM was significantly shorter in patients who had NDKD when compared to DNP.[8] Zhou and Chen in a diagnostic model developed to distinguish NDKD from DNP, also concluded that shorter duration of DM is associated with higher chances of NDKD.[17] We found that the severity of kidney failure predicts a nondiabetic lesion as compared with diabetic kidney disease, this is inconsistent with one study.[20] Other authors found no association between serum creatinine level and underlying kidney lesion,[18] whereas other found a strong relationship with the underlying pathology.[21],[22]

Our result along with a variety of existing literature supports a strong relationship between DRP and duration of DM with DNP. We concluded that the absence of DRP is strongly associated with the presence of NDRD, whereas the presence of DRP has a low sensitivity for the presence of DNP. The shorter the duration of diabetes the possibility of NDKD will be high.


   Acknowledgment Top


We acknowledge Mr. M. Ali Qureshi for his help in preparing and arranging the manuscript.

Conflict of interest:

None declared.

 
   References Top

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Unwin N, Whiting D, Gan D, Jacqmain O, Ghyoot G. International Diabetes Federation Diabetes Atlas. IDF Diabetes Atlas. Brussels, Belgium: International Diabetes Federation; 2009.  Back to cited text no. 1
    
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Ramachandran A, Ma RC, Snehalatha C. Diabetes in Asia. Lancet 2010;375:408-18.  Back to cited text no. 2
    
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Shera AS, Jawad F, Maqsood A. Prevalence of diabetes in Pakistan. Diabetes Res Clin Pract 2007;76:219-22.  Back to cited text no. 3
    
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Al-Wakeel JS, Hammad D, Al Suwaida A, Mitwalli AH, Memon NA, Sulimani F. Microvascular and macrovascular complications in diabetic nephropathy patients referred to nephrology clinic. Saudi J Kidney Dis Transpl 2009;20:77-85.  Back to cited text no. 4
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5.
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He F, Xia X, Wu XF, Yu XQ, Huang FX. Diabetic retinopathy in predicting diabetic nephropathy in patients with type 2 diabetes and renal disease: a meta-analysis. Diabetologia 2013;56:457-66.  Back to cited text no. 6
    
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Manaviat MR, Afkhami M, Shoja MR. Retinopathy and microalbuminuria in type II diabetic patients. BMC Ophthalmol 2004;4:9.  Back to cited text no. 7
    
8.
Liang S, Zhang XG, Cai GY, et al. Identifying parameters to distinguish non-diabetic renal diseases from diabetic nephropathy in patients with type 2 diabetes mellitus: a meta-analysis. PLoS One 2013;8:e64184.  Back to cited text no. 8
    
9.
Prakash J, Lodha M, Singh SK, Vohra R, Raja R, Usha. Diabetic retinopathy is a poor predictor of type of nephropathy in proteinuric type 2 diabetic patients. J Assoc Physicians India 2007;55:412-6.  Back to cited text no. 9
    
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Kramer CK, Retnakaran R. Concordance of retinopathy and nephropathy over time in Type 1 diabetes: an analysis of data from the Diabetes Control and Complications Trial. Diabet Med 2013;30:1333-41.  Back to cited text no. 10
    
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Chandy A, Pawar B, John M, Isaac R. Association between diabetic nephropathy and other diabetic microvascular and macrovascular complications. Saudi J Kidney Dis Transpl 2008;19:924-8.  Back to cited text no. 11
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12.
Parving HH, Hommel E, Mathiesen E, et al. Prevalence of microalbuminuria, arterial hypertension, retinopathy and neuropathy in patients with insulin dependent diabetes. Br Med J (Clin Res Ed) 1988;296:156-60.  Back to cited text no. 12
    
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Orchard TJ, Dorman JS, Maser RE, et al. Prevalence of complications in IDDM by sex and duration. Pittsburgh Epidemiology of Diabetes Complications Study II. Diabetes 1990;39:1116-24.  Back to cited text no. 13
    
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Christensen PK, Larsen S, Horn T, Olsen S, Parving HH. Causes of albuminuria in patients with type 2 diabetes without diabetic retinopathy. Kidney Int 2000;58:1719-31.  Back to cited text no. 14
    
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Tone A, Shikata K, Matsuda M, et al. Clinical features of non-diabetic renal diseases in patients with type 2 diabetes. Diabetes Res Clin Pract 2005;69:237-42.  Back to cited text no. 15
    
16.
Chong YB, Keng TC, Tan LP, et al. Clinical predictors of non-diabetic renal disease and role of renal biopsy in diabetic patients with renal involvement: a single centre review. Ren Fail 2012;34:323-8.  Back to cited text no. 16
    
17.
Zhou J, Chen X, Xie Y, Li J, Yamanaka N, Tong X. A differential diagnostic model of diabetic nephropathy and non-diabetic renal diseases. Nephrol Dial Transplant 2008;23: 1940-5.  Back to cited text no. 17
    
18.
Mak SK, Gwi E, Chan KW, et al. Clinical predictors of non-diabetic renal disease in patients with non-insulin dependent diabetes mellitus. Nephrol Dial Transplant 1997;12: 2588-91.  Back to cited text no. 18
    
19.
Kanauchi M, Kawano T, Uyama H, Shiiki H, Dohi K. Discordance between retinopathy and nephropathy in type 2 diabetes. Nephron 1998; 80:171-4.  Back to cited text no. 19
    
20.
Soni SS, Gowrishankar S, Kishan AG, Raman A. Non diabetic renal disease in type 2 diabetes mellitus. Nephrology (Carlton) 2006; 11:533-7.  Back to cited text no. 20
    
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Matias P, Viana H, Carvalho F, Ribeiro Santos J. Diabetes mellitus and renal disease: When to perform a renal biopsy? Port J Nephrol Hypert 2009;23(2):167-73.  Back to cited text no. 21
    
22.
Yaqub S, Kashif W, Hussain SA. Non-diabetic renal disease in patients with type-2 diabetes mellitus. Saudi J Kidney Dis Transplant 2012; 23:1000.  Back to cited text no. 22
    

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Correspondence Address:
Salman Imtiaz
Department of Nephrology, Dorab Patel Post Graduate Training and Research Center, The Kidney Center Post Graduate Training Institute, Karachi
Pakistan
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DOI: 10.4103/1319-2442.202794

PMID: 28352012

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