|
 
 |
| ORIGINAL ARTICLE |
|
| Year : 2017 | Volume
: 4
| Issue : 1 | Page : 21-25 |
|
Nondiabetic renal disease in type 2 diabetes mellitus
Lakshminarayana R Gopaliah1, Sheetal G Lakshminarayana2, Seethalekshmy Vijayan Nalumakkal3
1 Department of Nephrology, EMS Memorial Cooperative Hospital and Research Centre, Malappuram, Kerala, India
2 Department of Physiology, MES Medical College, Malappuram, Kerala, India
3 Department of Pathology, Amrita Institute of Medical Sciences and Research Centre, Kochi, Kerala, India
| Date of Web Publication | 1-Mar-2017 |
Correspondence Address:
Lakshminarayana R Gopaliah
Department of Nephrology, EMS Memorial Cooperative Hospital and Research Centre, Perinthalmanna, Malappuram - 679 322, Kerala
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/jina.jina_33_16
Background and Objectives: The prevalence of nondiabetic renal disease (NDRD) in those with type 2 diabetes mellitus (T2DM) is common worldwide; however, data from India are limited. Materials and Methods: This study included participants with T2DM who underwent renal biopsy with suspicion of NDRD from September 2009 to August 2016. Results: Seventy-one participants (males: 47 [66.2%] and females: 24 [33.8%]) of T2DM with mean age and standard deviation of 52.93 ± 12.56 years were included in the study. The indications for renal biopsy included acute on chronic renal failure in 35.2% (25), nephrotic syndrome in 31% (22), acute renal failure in 14.1% (10), nephritic syndrome in 14.1% (10), and others in 5.6% (4) of participants. The prevalence rates of NDRD, diabetic nephropathy (DN), and DN with NDRD were 50.71% (36), 28.16% (20), and 21.13% (15), respectively. Among the participants with NDRD, 69.44% (25) had primary glomerular diseases (PGDs), 16.67% (6) had tubulointerstitial diseases (TIDs), and 13.89% (5) had secondary glomerular diseases (SGDs). IgA nephropathy was the most common of PGDs affecting 28% (7), followed by postinfective glomerulonephritis (PIGN) in 20% (5), membranous nephropathy in 16% (4), focal segmental glomerulosclerosis in 12% (3), and miscellaneous lesions in 24% (10). Acute interstitial nephritis and primary amyloidosis were the most common of TIDs and SGDs, respectively. Among the patients with combination of DN with NDRD, 53.33% (8) were TIDs and 46.67% (7) had glomerular diseases. Acute tubular injury/necrosis and PIGN were the most common of TIDs and glomerular disease, respectively. The figures in brackets representing number of patients. Conclusions: The majority of the participants with T2DM had NDRD either alone or in combination with DN in the study, underlining the utility of renal biopsy for their diagnoses in those with appropriate indication. Wide spectrum of PGDs, TIDs, and SGDs was found in the study. Keywords: Diabetic nephropathy, nondiabetic renal disease, type 2 diabetes mellitus
How to cite this article:
Gopaliah LR, Lakshminarayana SG, Nalumakkal SV. Nondiabetic renal disease in type 2 diabetes mellitus. J Integr Nephrol Androl 2017;4:21-5 |
| Introduction | |  |
Renal diseases in 95% of patients with type 1 diabetes mellitus for over 10 years in the presence of diabetic retinopathy or neuropathy are most likely to be diabetic nephropathy (DN).[1] However, in type 2 diabetes mellitus (T2DM), 12–82% of them had renal lesions were due to nondiabetic renal diseases (NDRD) in different series.[2],[3],[4],[5],[6],[7],[8],[9],[10],[11] The end-stage renal disease in T2DM is due to NDRD in 40–60% of cases, thereby stressing the importance of early diagnosis.[10] The markers indicating the presence of NDRD include short duration of DM, unexplained worsening of renal disease, absence of neuropathy, absence of retinopathy and presence of active urinary sediments, or features of other systemic diseases.[9],[10],[11]
Aims and objectives
The present study was designed to retrospectively analyze kidney biopsies of patients with DM with the aim to find out the prevalence of DN, NDRD, and DN plus NDRD.
| Materials and Methods | | |
This is a retrospective study which included all consecutive patients with T2DM who underwent renal biopsies from September 2009 to August 2016, under guidance of ultrasound using Bard ® Max-Core ® disposable core biopsy instrument, CR Bard Inc., USA. All the biopsies were analyzed by light microscopy using hematoxylin and eosin, periodic acid–Schiff, Jone's silver methenamine, and Gomori's trichrome stains (MT), and immunofluorescence (IF) studies were performed using antihuman IgG, IgA, IgM, C3, C1q, kappa, and lambda light chains. The IF analysis was done using anti-mouse IgG (whole molecule)-fluorescein isothiocyanate antibody sourced from goat on frozen sections.
The diagnosis of diabetes mellitus was made according to the criteria stated by the American Diabetes Association. Onset of diabetes was defined as the time when T2DM was first diagnosed. Duration of T2DM was defined as the period between the age of onset and renal biopsy.
The indications for renal biopsy were: acute on chronic renal failure (ACRF), nephrotic syndrome (NS), acute renal failure (ARF), nephritic syndrome, rapidly progressive renal failure, and subnephrotic proteinuria.
ACRF was diagnosed if there was a rapid decline of renal function characterized by progressive decline in glomerular filtration rate manifested by increasing serum creatinine or oliguria or need for dialysis in stable case of chronic kidney disease. Patients underwent renal biopsy after exclusion of prerenal, obvious intrarenal lesions such as acute pyelonephritis, accelerated hypertension, and postrenal causes for acute worsening of renal function.
DN was diagnosed by the presence of mesangial expansion, with or without the nodular Kimmelstiel–Wilson formation, basement membrane thickening, fibrin caps, or capsular drops and presence of pseudolinear pattern on IF. NDRDs were diagnosed and categorized as per standard guidelines.[12]
The protocol was submitted to the Institutional Ethical Committee and was approved as it was retrospective study without any added cost to the patients or the institution.
The data were analyzed by SPSS version 17 for Windows, by SPSS Inc., Chicago, IL, USA. Two-sided P < 0.05 was considered as statistically significant. The observations were analyzed and presented as mean, standard deviation, percentage, and patient number as per relevance. Statistical tests used were Pearson's Chi-square test and Fisher's exact test as applicable in the analysis. The P < 0.05 (two-sided) was considered as statistically significant.
| Results | | |
A total 71 patients (males: 47 [66.2%] and females: 24 [33.8%], mean age: 52.93 years) of DM underwent renal biopsy, with a suspicion of NDRD. The demographic data of number of participants, mean age, gender, and duration of T2DM are summarized in [Table 1]. The prevalence of different histologies is presented as percentages followed by figures in brackets representing number of patients diagnosed with the type of lesion.{Table 1}
The prevalence rates of NDRD, DN, and DN with NDRD were 50.71% (36), 28.16% (20), and 21.13% (15), respectively [Figure 1]. The mean age, gender, duration of T2DM, and number of participants with DN, DN + NDRD, and NDRD are summarized in [Table 2]. The mean duration of T2DM was 12.45, 12.13, and 5.33 years in participants with DN, DN + NDRD, and NDRD, respectively. The duration of T2DM in participants with DN or DN + NDRD was higher than those with NDRD, statistically significant (Pearson χ2 = 29.95 and P = 0.038). The gender and age of the participants did not have any statistically significant effect on renal pathology (P > 0.05). | Figure 1: Broad categorization according to renal histology in participants with type 2 diabetes mellitus. DN: Diabetic nephropathy; NDRD: Nondiabetic renal diseases
Click here to view |
 | Table 1: The demographic data of participants with type 2 diabetes mellitus
Click here to view |
Nondiabetic renal disease
NDRD was found in 50.71% (36 of 71) of participants.
Among the participants with NDRD, 69.44% (25) had primary glomerular diseases (PGDs), 16.67% (6) had tubulointerstitial diseases (TIDs), and 13.89% (5) had secondary glomerular diseases (SGDs). IgA nephropathy (IgAN) was the most common among PGDs affecting 28% (7) of participants, followed by postinfective glomerulonephritis (PIGN) in 20% (5), membranous nephropathy (MN) in 16% (4), focal segmental glomerulosclerosis (FSGS) in 12% (3), chronic glomerulonephritis (CGN) in 8% (2), membranoproliferative glomerulonephritis (MPGN) in 8% (2), IgM nephropathy (IgMN) in 4% (1), and minimal change disease (MCD) in 4% (1). All the cases of PIGN in the study were characterized by low C3 and normal C4 and were secondary to infections.
Acute interstitial nephritis (AIN) was the most common among TIDs found in 50% (3) of participants, followed by chronic tubulointerstitial nephritis (CTIN) in 33.33% (2) and cast nephropathy in 16.67% (1).
Primary amyloidosis was the most common among SGDs affecting 40% (2), followed by nonamyloid deposition disease 20% (1), antineutrophil cytoplasmic antibody (ANCA) related pauci-immune glomerulonephritis in 20% (1), and anti-glomerular basement membrane disease in 20% (1).
Diabetic nephropathy
The isolated DN was found in 28.16% (20 of 71) of participants and was diagnosed by presence characteristics as described in methods.
Diabetic nephropathy with associated nondiabetic renal disease
DN with associated NDRD was found in 21.13% (15 of 71) of participants, of which 53.33% (8) were TIDs and 46.67% (7) had glomerular diseases. Acute tubular injury/necrosis (ATN) was the most common TIDs affecting 62.5% (5), followed by CTIN in 25% (2) and acute pyelonephritis (APN) 12.5% (1) of participants. PIGN was the most common glomerular disease affecting 57.14% (4) of participants, followed by IgAN in 14.28% (1), antidisease in 14.28% (1), and ANCA-related pauci-immune glomerulonephritis in 14.28% (1).
Relation of indication of renal biopsy with histology
The most common indication for biopsy was ACRF in 35.2% (25), followed by NS in 31% (22), ARF in 14.1% (10), acute nephritic syndrome (ANS) in 14.1% (10), rapidly progressive glomerulonephritis (RPGN) in 4.2% (3), and subnephrotic proteinuria in 1.4% (1) [Figure 2]. The clinical syndromes and histological diagnosis are summarized in [Figure 3]. | Figure 2: Indications for renal biopsy (number of participants and percentage)
Click here to view |
PIGN was the most common pathology followed by CTIN, IgAN, CGN, AIN, ATN, and APN in participants who underwent renal biopsy for ACRF. DN was the most common cause for presentation as NS in T2DM followed by MN, FSGS, amyloidosis, MCD, IgMN, and nonamyloid deposition disease. ATN was the most common cause of ARF followed by AIN, IgAN, MPGN, and cast nephropathy. PIGN and IgAN were the most common causes for ANS followed by MPGN. The ANCA-related pauci-immune GN and anti-GBM disease were the causes of RPGN, and one participant who underwent biopsy for subnephrotic proteinuria had IgAN. The relation of syndromic diagnosis with renal histology was statistically significant (Pearson χ2 = 34.27 and P < 0.01).
| Discussion | | |
The majority of patients whose history and clinical findings are compatible with diabetic kidney disease do not benefit from kidney biopsy because the diagnosis and treatment is usually not altered.[1] However, renal biopsy is helpful in diagnosis and treatment of NDRD in those with T2DM.[2],[3],[4],[5],[6],[7],[8],[9],[10],[11] The clues for NDRD in T2DM are the presence of active urinary sediments, low complement levels, sudden deterioration of renal function, nephrotic proteinuria without retinopathy or neuropathy, impaired renal function with normal and/or low grade of proteinuria, absence of retinopathy, and short duration of diabetes.[9],[10],[11]
In the present study, the prevalence rates of NDRD, DN, and DN with NDRD were 50.71%, 28.16%, and 21.13%, respectively. Observations of our study are similar with earlier reports of renal biopsies in patients with T2DM. The prevalence rates of NDRD, DN, and NDRD + ND varied from 24.73% to 82.9%, 6.5% to 66%, and 4% to 44.08%, respectively, in earlier studies.[2],[3],[4],[5],[7],[8],[9] The variations in percentages are due to heterogeneity of participants and indications for biopsies. In one study reported from South India, 50% of the participants had NDRD and remaining had DN.[6]
The most common NDRDs varied in different studies, due to variations in biopsy policies, geographic and ethnic factors. TIDs were the most common NDRD in two earlier studies [7],[9] and proliferative GN as the most common in one [5] and MN in another study.[6]
PGDs were the most common cause for NDRD in the present study, with the four most common being IgAN, PIGN, MN, and FSGS. Almost all types of PGDs have been reported in the literature.[2],[3],[4],[5],[6],[7],[8],[9],[10],[11] FSGS, IgAN, MN, PIGN, and MCD were the most common PGDs, respectively, in earlier studies.[3], 4, [6],[7],[8]
Primary amyloidosis was the most common SGDs, followed by ANCA-related pauci-immune glomerulonephritis and nonamyloid deposition disease in the present study, whereas lupus nephritis was the most common in an earlier study.[8]
DN with superimposed NDRD was found in 21.13% of participants, with ATIN and PIGN being the two common associated lesions in the present study. The prevalence of NDRD superimposed on DN was varied widely (4–41%) in earlier studies.[3],[7],[8],[9] IgAN and MN were the most prevalent lesions found in patients with DN in one of the studies.[3]
The most common indication for biopsy in the study was ACRF followed by NS, ARF, ANS, RPGN, and subnephrotic proteinuria. The reported indications for biopsies in earlier reports were similar to the present study, which included NS, ARF, RPRF, absence of retinopathy, hematuria, and ACRF.[2],[4],[7],[8],[9]
Limitations
The smaller sample size and absence of electron microscopic evaluation are two major limitations of the study.
| Conclusions | | |
The prevalence of NDRD in T2DM is high in our population, especially in participants who underwent renal biopsy due to the presence with atypical features. The prevalence rates of NDRD, DN, and NDRD superimposed on DN were 50.71%, 28.16%, and 21.13%, respectively. NDRDs are the cause NS in up to 48% of cases. PGDs were the most common cause for NDRD, followed by TIDs. Among the PGDs, IgAN, PIGN, MN, and FSGS were common. ATN was the most common TID followed by AIN. ATN followed by PIGN was the two most NDRD to be associated in those with underlying DN. The mean duration of T2DM was higher in participants with DN or DN with superimposed NDRD than those with isolated NDRD.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Mogensen CE, Christensen CK. Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med 1984;311:89-93.  |
| 2. | Lai CP, Chang CC, Yang Y, Wen YK, Chiou PF, Chen M, et al. Non-diabetic renal diseases in type 2 diabetic patients with renal involvement: Clinicopathological study in a single medical center in Taiwan. Acta Nephrologica 2010;24:157-66. |
| 3. | Pham TT, Sim JJ, Kujubu DA, Liu IL, Kumar VA. Prevalence of nondiabetic renal disease in diabetic patients. Am J Nephrol 2007;27:322-8. |
| 4. | Zhuo L, Ren W, Li W, Zou G, Lu J. Evaluation of renal biopsies in type 2 diabetic patients with kidney disease: A clinicopathological study of 216 cases. Int Urol Nephrol 2013;45:173-9. |
| 5. | John GT, Date A, Korula A, Jeyaseelan L, Shastry JC, Jacob CK. Nondiabetic renal disease in noninsulin-dependent diabetics in a South Indian Hospital. Nephron 1994;67:441-3. |
| 6. | Premalatha G, Vidhya K, Deepa R, Ravikumar R, Rema M, Mohan V. Prevalence of non-diabetic renal disease in type 2 diabetic patients in a diabetes centre in Southern India. J Assoc Physicians India 2002;50:1135-9. |
| 7. | Soni SS, Gowrishankar S, Kishan AG, Raman A. Non diabetic renal disease in type 2 diabetes mellitus. Nephrology (Carlton) 2006;11:533-7. |
| 8. | Das U, Dakshinamurty KV, Prayaga A, Uppin MS. Nondiabetic kidney disease in type 2 diabetic patients: A single center experience. Indian J Nephrol 2012;22:358-62. [ PUBMED]  |
| 9. | Wilfred DC, Mysorekar VV, Venkataramana RS, Eshwarappa M, Subramanyan R. Nondiabetic renal disease in type 2 diabetes mellitus patients: A clinicopathological study. J Lab Physicians 2013;5:94-9. [ PUBMED] |
| 10. | Prakash J. Non-diabetic renal disease (NDRD) in patients with type 2 diabetes mellitus (type 2 DM). J Assoc Physicians India 2013;61:194-9. |
| 11. | Tone A, Shikata K, Matsuda M, Usui H, Okada S, Ogawa D, et al. Clinical features of non-diabetic renal diseases in patients with type 2 diabetes. Diabetes Res Clin Pract 2005;69:237-42. |
| 12. | Hebert LA, Parikh S, Prosek J, Nadasdy T, Rovin BH. Differential diagnosis of glomerular disease: A systematic and inclusive approach. Am J Nephrol 2013;38:253-66. |
[Figure 1], [Figure 2], [Figure 3]
[Table 2], [Table 2]
|
Search Pubmed for