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Guide : Dr Rekha Patil
Co Guide : Dr Dnyanesh Morkar
Presenter : Dr Prudhvi Krishna
Non-diabetic renal disease in type 2
diabetes mellitus: Study of renal - retinal
relationship
Indian Journal of nephrology August
2015
Introduction
▪ The incidence and prevalence of diabetes mellitus
(dm)are increasing
▪ Diabetes still remains the most common cause of ESKD
in the united states and in many other countries.
▪ Diabetic nephropathy (dn) is not the sole renal disease
in diabetic patients. Kidney diseases other than diabetic
nephropathy can occur in type 2 diabetic patients and
such kidney diseases are known as non-diabetic renal
disease (NDRD), either isolated or superimposed on
DN.
The occurrence of NDRD in diabetic
patients is reported in several
studies from around the world.[
Introduction
▪ DN is hard to reverse.
▪ However, certain NDRD, such as
mesangial-proliferative glomerulonephritis, IgA
nephropathy and membranous nephropathy, are often
treatable, even remittable.
▪ Thus, therapy and prognosis of DN and NDRD are
quite different. Therefore, differential diagnosis of
these two entities in diabetic patients is of
considerable importance.
AIM
▪ To analyze spectrum of nephropathy in
proteinuric type 2 diabetic patients and to study
the relationship between nephropathy and
retinopathy in patients with type 2 diabetes
mellitus (T2DM) with proteinuria.
AIM
▪ To analyze spectrum of nephropathy in
proteinuric type 2 diabetic patients and to study
the relationship between nephropathy and
retinopathy in patients with type 2 diabetes
mellitus (T2DM) with proteinuria.
Methodology
▪ This study was carried in the Department of Nephrology,
Banaras Hindu University, Varanasi, from October 2011
to September 2013.
▪ Diabetes was diagnosed as per WHO criteria.
▪ All type 2 diabetic patients of both gender attending the
nephrology services were screened for proteinuria.
▪ The urine was examined for detection of protein using
dipstick method. The patients with dipstick proteinuria of
1+ or more were subjected to quantitative 24-h urinary
protein.
Methodology
▪ Type 2 diabetic patients with proteinuria of more
than 1 g were included in this study.
▪ The duration between diagnosis of DM and
onset of renal manifestations were recorded in
individual patients.
▪ Patients with absence of voluntary consent,
contraindication to kidney biopsy and severe renal
failure (serum creatinine > 5 mg/dl) were excluded
from the study.
Methodology
▪ All patients were subjected to detailed
history,physical examination and laboratory
investigations.
▪ Ultrasonography was carried to assess kidney size,
cortical thickness and renal margin in each case.
▪ Single ophthalmologist examined optic fundi for
evidence of diabetic retinopathy (DR).
DN was diagnosed in the presence of..
Nodular or diffuse glomerulosclerosis
glomerular hypertrophy,
mesangial (diffuse or nodular) widening
glomerular capillary wall thickening
evidence of exudative lesions or fibrin caps
(i.e. hyaline material heaped up on the inner
side of the glomerular basement membrane)
and the presence of micro aneurysms of
glomerular capillaries.
The various NDRDs were diagnosed on the
basis of their characteristic features on light
microscopy.
Membranous nephropathy was diagnosed by
presence of diffuse and global capillary wall
thickening in the absence of significant glomerular
hypercellularity and increase in mesangial matrix.
In few glomeruli, deposits and spikes were also seen
at the outer surface of glomerular basement
membrane.
The various NDRDs were diagnosed on the
basis of their characteristic features on light
microscopy.
Focal segmental glomerulosclerosis was
diagnosed on findings of focal areas of consolidation
and otherwise normal pattern elsewhere with no
evidence suggestive of DN.
Amyloidosis was diagnosis was made by the
presence of hyaline material deposits in glomerular
basement membrane and mesangium and confirmed
by positive staining of material with Congo red stain.
The various NDRDs were diagnosed on the
basis of their characteristic features on light
microscopy.
Mesangio-proliferative glomerulonephritis was
diagnosed by the presence of increase in number of
mesangial cells and matrix without evidence of other
features of DN such as nodule formation, thickening
of glomerular basement membrane and intertubular
arteriolar hyalinosis or arteriolar hyalinosis.
Isolated NDRD was diagnosed in the absence of
histological features of DN.
Mixed lesions (NDRD superimposed above DN)
were diagnosed in the presence of histological
evidences of DN.
Results
Idiopathic
membranous
nephropathy – 4
Amyloidosis -2
Focal segmental
glomerulosclerosis -2
Focal
mesangio-proliferative
-1
Proliferative
glomerulonephritis
with vasculitis -1
Myeloma cast
nephropathy -1
Chronic
tubulo-interstitial
nephritis -1
Minimal change
disease -1
NDRD SUPERIMPOSED ON DN
▪ NDRD superimposed on DN was diffuse
proliferative glomerulonephritis (n-2).
▪ The other NDRD in this group included chronic
tubulo-interstitial nephritis, amyloidosis, minimal
change disease and crescentic GN, all consisting of
one case each.
DIABETIC RETINOPATHY
▪ Kidney histology in patients with DR (n-10) revealed
DN in 6 (60%), NDRD in 1 (10%) and mixed lesion
in 3 (30%) patients.
▪ Thus, absence of DR favors NDRD but does not
exclude DN because isolated DN was noted in
28.57% cases in absence of DR.
▪ Similarly biopsy proven NDRD (pure NDRD; 10%
and mixed lesion; 30%) was noted in 40% of cases
in presence of DR.
Conclusions
▪ All type 2 diabetic patients with clinical renal disease do
not have classical DN.
▪ Non-diabetic kidney disease either alone or
superimposed on DN were seen in 61.3% of diabetic
patients. We observed that longer duration (>10 years) of
diabetes was the strongest predictor of DN and diabetic
patients having NDRD alone had shorter duration of DM.
▪ DR was absent in 21/31 (67.7%) patients. Thus, retinal
lesion is less frequent in type 2 diabetes in comparison to
type 1 diabetes.
Conclusions
▪ Non-diabetic kidney disease was noted in 40% of the
cases in presence of DR and 43% of the cases had
biopsy proven DN in absence of DR.
▪ However, observed that the absence of retinopathy
favors NDRD but does not exclude occurrence of DN.
Therefore, DR does not predict nature of nephropathy in
patients with type 2 diabetes.
▪ Renal biopsy is necessary for precise diagnosis of
diabetic and non-diabetic kidney disease in type 2
diabetic patients with proteinuria.
Non‑diabetic renal disease in type 2 diabetes mellitus: Study of renal - retinal relationship

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Non‑diabetic renal disease in type 2 diabetes mellitus: Study of renal - retinal relationship

  • 1. Guide : Dr Rekha Patil Co Guide : Dr Dnyanesh Morkar Presenter : Dr Prudhvi Krishna Non-diabetic renal disease in type 2 diabetes mellitus: Study of renal - retinal relationship Indian Journal of nephrology August 2015
  • 2. Introduction ▪ The incidence and prevalence of diabetes mellitus (dm)are increasing ▪ Diabetes still remains the most common cause of ESKD in the united states and in many other countries. ▪ Diabetic nephropathy (dn) is not the sole renal disease in diabetic patients. Kidney diseases other than diabetic nephropathy can occur in type 2 diabetic patients and such kidney diseases are known as non-diabetic renal disease (NDRD), either isolated or superimposed on DN.
  • 3. The occurrence of NDRD in diabetic patients is reported in several studies from around the world.[
  • 4. Introduction ▪ DN is hard to reverse. ▪ However, certain NDRD, such as mesangial-proliferative glomerulonephritis, IgA nephropathy and membranous nephropathy, are often treatable, even remittable. ▪ Thus, therapy and prognosis of DN and NDRD are quite different. Therefore, differential diagnosis of these two entities in diabetic patients is of considerable importance.
  • 5. AIM ▪ To analyze spectrum of nephropathy in proteinuric type 2 diabetic patients and to study the relationship between nephropathy and retinopathy in patients with type 2 diabetes mellitus (T2DM) with proteinuria.
  • 6. AIM ▪ To analyze spectrum of nephropathy in proteinuric type 2 diabetic patients and to study the relationship between nephropathy and retinopathy in patients with type 2 diabetes mellitus (T2DM) with proteinuria.
  • 7. Methodology ▪ This study was carried in the Department of Nephrology, Banaras Hindu University, Varanasi, from October 2011 to September 2013. ▪ Diabetes was diagnosed as per WHO criteria. ▪ All type 2 diabetic patients of both gender attending the nephrology services were screened for proteinuria. ▪ The urine was examined for detection of protein using dipstick method. The patients with dipstick proteinuria of 1+ or more were subjected to quantitative 24-h urinary protein.
  • 8. Methodology ▪ Type 2 diabetic patients with proteinuria of more than 1 g were included in this study. ▪ The duration between diagnosis of DM and onset of renal manifestations were recorded in individual patients. ▪ Patients with absence of voluntary consent, contraindication to kidney biopsy and severe renal failure (serum creatinine > 5 mg/dl) were excluded from the study.
  • 9. Methodology ▪ All patients were subjected to detailed history,physical examination and laboratory investigations. ▪ Ultrasonography was carried to assess kidney size, cortical thickness and renal margin in each case. ▪ Single ophthalmologist examined optic fundi for evidence of diabetic retinopathy (DR).
  • 10. DN was diagnosed in the presence of.. Nodular or diffuse glomerulosclerosis glomerular hypertrophy, mesangial (diffuse or nodular) widening glomerular capillary wall thickening evidence of exudative lesions or fibrin caps (i.e. hyaline material heaped up on the inner side of the glomerular basement membrane) and the presence of micro aneurysms of glomerular capillaries.
  • 11. The various NDRDs were diagnosed on the basis of their characteristic features on light microscopy. Membranous nephropathy was diagnosed by presence of diffuse and global capillary wall thickening in the absence of significant glomerular hypercellularity and increase in mesangial matrix. In few glomeruli, deposits and spikes were also seen at the outer surface of glomerular basement membrane.
  • 12. The various NDRDs were diagnosed on the basis of their characteristic features on light microscopy. Focal segmental glomerulosclerosis was diagnosed on findings of focal areas of consolidation and otherwise normal pattern elsewhere with no evidence suggestive of DN. Amyloidosis was diagnosis was made by the presence of hyaline material deposits in glomerular basement membrane and mesangium and confirmed by positive staining of material with Congo red stain.
  • 13. The various NDRDs were diagnosed on the basis of their characteristic features on light microscopy. Mesangio-proliferative glomerulonephritis was diagnosed by the presence of increase in number of mesangial cells and matrix without evidence of other features of DN such as nodule formation, thickening of glomerular basement membrane and intertubular arteriolar hyalinosis or arteriolar hyalinosis. Isolated NDRD was diagnosed in the absence of histological features of DN. Mixed lesions (NDRD superimposed above DN) were diagnosed in the presence of histological evidences of DN.
  • 14.
  • 15. Results Idiopathic membranous nephropathy – 4 Amyloidosis -2 Focal segmental glomerulosclerosis -2 Focal mesangio-proliferative -1 Proliferative glomerulonephritis with vasculitis -1 Myeloma cast nephropathy -1 Chronic tubulo-interstitial nephritis -1 Minimal change disease -1
  • 16. NDRD SUPERIMPOSED ON DN ▪ NDRD superimposed on DN was diffuse proliferative glomerulonephritis (n-2). ▪ The other NDRD in this group included chronic tubulo-interstitial nephritis, amyloidosis, minimal change disease and crescentic GN, all consisting of one case each.
  • 18. ▪ Kidney histology in patients with DR (n-10) revealed DN in 6 (60%), NDRD in 1 (10%) and mixed lesion in 3 (30%) patients. ▪ Thus, absence of DR favors NDRD but does not exclude DN because isolated DN was noted in 28.57% cases in absence of DR. ▪ Similarly biopsy proven NDRD (pure NDRD; 10% and mixed lesion; 30%) was noted in 40% of cases in presence of DR.
  • 19. Conclusions ▪ All type 2 diabetic patients with clinical renal disease do not have classical DN. ▪ Non-diabetic kidney disease either alone or superimposed on DN were seen in 61.3% of diabetic patients. We observed that longer duration (>10 years) of diabetes was the strongest predictor of DN and diabetic patients having NDRD alone had shorter duration of DM. ▪ DR was absent in 21/31 (67.7%) patients. Thus, retinal lesion is less frequent in type 2 diabetes in comparison to type 1 diabetes.
  • 20. Conclusions ▪ Non-diabetic kidney disease was noted in 40% of the cases in presence of DR and 43% of the cases had biopsy proven DN in absence of DR. ▪ However, observed that the absence of retinopathy favors NDRD but does not exclude occurrence of DN. Therefore, DR does not predict nature of nephropathy in patients with type 2 diabetes. ▪ Renal biopsy is necessary for precise diagnosis of diabetic and non-diabetic kidney disease in type 2 diabetic patients with proteinuria.

Editor's Notes

  1. C  Congestive heart failure (or Left ventricular systolic dysfunction)1 H Hypertension: blood pressure consistently above 140/90 mmHg (or treated hypertension on medication)1 A2 Age ≥75 years2 D Diabetes Mellitus1 S2 Prior Stroke or TIA or thromboembolism2 V Vascular disease (e.g. peripheral artery disease, myocardial infarction, aortic plaque)1 A Age 65–74 years1 Sc Sex category (i.e. female sex)1 The European Society of Cardiology (ESC) and National Institute for Health and Care Excellence (NICE) guidelines recommend that if the patient has a CHA2DS2-VASc score of 2 and above, oral anticoagulation therapy (OAC) with a Vitamin K Antagonist (VKA, e.g. warfarin with target INR of 2-3) or one of the non-VKA oral anticoagulant drugs (NOACs, e.g. dabigatran, rivaroxaban, edoxaban, or apixaban) is recommended.
  2. C  Congestive heart failure (or Left ventricular systolic dysfunction)1 H Hypertension: blood pressure consistently above 140/90 mmHg (or treated hypertension on medication)1 A2 Age ≥75 years2 D Diabetes Mellitus1 S2 Prior Stroke or TIA or thromboembolism2 V Vascular disease (e.g. peripheral artery disease, myocardial infarction, aortic plaque)1 A Age 65–74 years1 Sc Sex category (i.e. female sex)1 The European Society of Cardiology (ESC) and National Institute for Health and Care Excellence (NICE) guidelines recommend that if the patient has a CHA2DS2-VASc score of 2 and above, oral anticoagulation therapy (OAC) with a Vitamin K Antagonist (VKA, e.g. warfarin with target INR of 2-3) or one of the non-VKA oral anticoagulant drugs (NOACs, e.g. dabigatran, rivaroxaban, edoxaban, or apixaban) is recommended.
  3. DR was classified into two groups.that is, non‑proliferative DR (NPDR) and proliferative DR (PDR). NPDR was diagnosed in the presence of microaneurysm, dot blot or flame‑shaped hemorrhage, hard exudates, or evidence of macular edema. The PDR was diagnosed in the presence of new vessels formation or pre‑retinal or vitreous hemorrhage.
  4. C  Congestive heart failure (or Left ventricular systolic dysfunction)1 H Hypertension: blood pressure consistently above 140/90 mmHg (or treated hypertension on medication)1 A2 Age ≥75 years2 D Diabetes Mellitus1 S2 Prior Stroke or TIA or thromboembolism2 V Vascular disease (e.g. peripheral artery disease, myocardial infarction, aortic plaque)1 A Age 65–74 years1 Sc Sex category (i.e. female sex)1 The European Society of Cardiology (ESC) and National Institute for Health and Care Excellence (NICE) guidelines recommend that if the patient has a CHA2DS2-VASc score of 2 and above, oral anticoagulation therapy (OAC) with a Vitamin K Antagonist (VKA, e.g. warfarin with target INR of 2-3) or one of the non-VKA oral anticoagulant drugs (NOACs, e.g. dabigatran, rivaroxaban, edoxaban, or apixaban) is recommended.
  5. C  Congestive heart failure (or Left ventricular systolic dysfunction)1 H Hypertension: blood pressure consistently above 140/90 mmHg (or treated hypertension on medication)1 A2 Age ≥75 years2 D Diabetes Mellitus1 S2 Prior Stroke or TIA or thromboembolism2 V Vascular disease (e.g. peripheral artery disease, myocardial infarction, aortic plaque)1 A Age 65–74 years1 Sc Sex category (i.e. female sex)1 The European Society of Cardiology (ESC) and National Institute for Health and Care Excellence (NICE) guidelines recommend that if the patient has a CHA2DS2-VASc score of 2 and above, oral anticoagulation therapy (OAC) with a Vitamin K Antagonist (VKA, e.g. warfarin with target INR of 2-3) or one of the non-VKA oral anticoagulant drugs (NOACs, e.g. dabigatran, rivaroxaban, edoxaban, or apixaban) is recommended.
  6. C  Congestive heart failure (or Left ventricular systolic dysfunction)1 H Hypertension: blood pressure consistently above 140/90 mmHg (or treated hypertension on medication)1 A2 Age ≥75 years2 D Diabetes Mellitus1 S2 Prior Stroke or TIA or thromboembolism2 V Vascular disease (e.g. peripheral artery disease, myocardial infarction, aortic plaque)1 A Age 65–74 years1 Sc Sex category (i.e. female sex)1 The European Society of Cardiology (ESC) and National Institute for Health and Care Excellence (NICE) guidelines recommend that if the patient has a CHA2DS2-VASc score of 2 and above, oral anticoagulation therapy (OAC) with a Vitamin K Antagonist (VKA, e.g. warfarin with target INR of 2-3) or one of the non-VKA oral anticoagulant drugs (NOACs, e.g. dabigatran, rivaroxaban, edoxaban, or apixaban) is recommended.
  7. C  Congestive heart failure (or Left ventricular systolic dysfunction)1 H Hypertension: blood pressure consistently above 140/90 mmHg (or treated hypertension on medication)1 A2 Age ≥75 years2 D Diabetes Mellitus1 S2 Prior Stroke or TIA or thromboembolism2 V Vascular disease (e.g. peripheral artery disease, myocardial infarction, aortic plaque)1 A Age 65–74 years1 Sc Sex category (i.e. female sex)1 The European Society of Cardiology (ESC) and National Institute for Health and Care Excellence (NICE) guidelines recommend that if the patient has a CHA2DS2-VASc score of 2 and above, oral anticoagulation therapy (OAC) with a Vitamin K Antagonist (VKA, e.g. warfarin with target INR of 2-3) or one of the non-VKA oral anticoagulant drugs (NOACs, e.g. dabigatran, rivaroxaban, edoxaban, or apixaban) is recommended.
  8. C  Congestive heart failure (or Left ventricular systolic dysfunction)1 H Hypertension: blood pressure consistently above 140/90 mmHg (or treated hypertension on medication)1 A2 Age ≥75 years2 D Diabetes Mellitus1 S2 Prior Stroke or TIA or thromboembolism2 V Vascular disease (e.g. peripheral artery disease, myocardial infarction, aortic plaque)1 A Age 65–74 years1 Sc Sex category (i.e. female sex)1 The European Society of Cardiology (ESC) and National Institute for Health and Care Excellence (NICE) guidelines recommend that if the patient has a CHA2DS2-VASc score of 2 and above, oral anticoagulation therapy (OAC) with a Vitamin K Antagonist (VKA, e.g. warfarin with target INR of 2-3) or one of the non-VKA oral anticoagulant drugs (NOACs, e.g. dabigatran, rivaroxaban, edoxaban, or apixaban) is recommended.
  9. C  Congestive heart failure (or Left ventricular systolic dysfunction)1 H Hypertension: blood pressure consistently above 140/90 mmHg (or treated hypertension on medication)1 A2 Age ≥75 years2 D Diabetes Mellitus1 S2 Prior Stroke or TIA or thromboembolism2 V Vascular disease (e.g. peripheral artery disease, myocardial infarction, aortic plaque)1 A Age 65–74 years1 Sc Sex category (i.e. female sex)1 The European Society of Cardiology (ESC) and National Institute for Health and Care Excellence (NICE) guidelines recommend that if the patient has a CHA2DS2-VASc score of 2 and above, oral anticoagulation therapy (OAC) with a Vitamin K Antagonist (VKA, e.g. warfarin with target INR of 2-3) or one of the non-VKA oral anticoagulant drugs (NOACs, e.g. dabigatran, rivaroxaban, edoxaban, or apixaban) is recommended.
  10. C  Congestive heart failure (or Left ventricular systolic dysfunction)1 H Hypertension: blood pressure consistently above 140/90 mmHg (or treated hypertension on medication)1 A2 Age ≥75 years2 D Diabetes Mellitus1 S2 Prior Stroke or TIA or thromboembolism2 V Vascular disease (e.g. peripheral artery disease, myocardial infarction, aortic plaque)1 A Age 65–74 years1 Sc Sex category (i.e. female sex)1 The European Society of Cardiology (ESC) and National Institute for Health and Care Excellence (NICE) guidelines recommend that if the patient has a CHA2DS2-VASc score of 2 and above, oral anticoagulation therapy (OAC) with a Vitamin K Antagonist (VKA, e.g. warfarin with target INR of 2-3) or one of the non-VKA oral anticoagulant drugs (NOACs, e.g. dabigatran, rivaroxaban, edoxaban, or apixaban) is recommended.
  11. C  Congestive heart failure (or Left ventricular systolic dysfunction)1 H Hypertension: blood pressure consistently above 140/90 mmHg (or treated hypertension on medication)1 A2 Age ≥75 years2 D Diabetes Mellitus1 S2 Prior Stroke or TIA or thromboembolism2 V Vascular disease (e.g. peripheral artery disease, myocardial infarction, aortic plaque)1 A Age 65–74 years1 Sc Sex category (i.e. female sex)1 The European Society of Cardiology (ESC) and National Institute for Health and Care Excellence (NICE) guidelines recommend that if the patient has a CHA2DS2-VASc score of 2 and above, oral anticoagulation therapy (OAC) with a Vitamin K Antagonist (VKA, e.g. warfarin with target INR of 2-3) or one of the non-VKA oral anticoagulant drugs (NOACs, e.g. dabigatran, rivaroxaban, edoxaban, or apixaban) is recommended.