• To start with ,Diabetic nephropathy and diabetic retinopathy are two important microvascular complications of diabetes 
• They both progresses to results in similar conditions such as End stage renal disease and blindness which can be treated 
• Apart from these conditions people as well as the healthcare system might suffer economically and socially
• Studies show  that both types of diabetic patients have the risk of diabetic nephropathy and retinopathy with less prevalence in type 2 when compared with type 1DM

Relation between diabetic nephropathy and retinopathy

• Patients with nephropathy and T1DM always have retinopathy
• The histological changes in the glomeruli and increased protein excretion is evident in advanced stages 
• Increased levels of BUN,creatinine , proteinuria or microalbuminuria  are the early indicators of retinopathy
• The connection is less in patients with T2DM
• Type 2 diabetic with marked proteinuria and retinopathy have Diabetic nephropathy,and in those without have high chances of non diabetic glomerular disease 

I.Diabetic Nephropathy 

• It is a clinical syndrome which is characterized by the persistent albuminuria, increased arterial blood pressure, decrease in glomerular filtration rate and increased risk of cardiovascular mortality and morbidity 

• It is an major cause for end stage renal disease 
• The  type of diabetes associated with it is type II in majority of population
• Early detection and treatments are planned according to the condition of the patient. If not, the patient may develop cardiac issues and ultimately can lead to death before reaching the end stage renal disease.
• Diabetic nephropathy is defined as the presence of proteinuria in a person with diabetes presents.
• The albumin concentration is equal to 300 mg/L to present the positive results over dipstick method indicate the presence of protein in urine 
• Greater than 300 mg/L of albuminuria is known as clinical or overt nephropathy
• Greater than or Less than 200 micrograms /min (300 mg/ L)represents incipient nephropathy or microalbuminuria .These group of people can have high risk of End stage renal disease in the near future ,but most of them (about 25-30%) could revert back to normal if glycemic control is optimized 

Who is at risk?

• The long-term presence of diabetes will be a major risk for the development of nephropathy 
• Due to better management and treatment the diabetic nephropathy is declining in type 1 patients 
• Why type 2 is the question? As we know that the duration of the condition is cause of the disease ,so when considered this the precise and exact  onset of type 2 diabetes is not known which is why it is hard to control 
• The risk is equal in both males and females 
• The rate of complications are more likely to be evident in 15-45% of patients with type 1 diabetes mellitus and only less than 20% in type 2 diabetic patients
• The major risk factors include 

• Increased Blood pressure 
• Poor glycemic control 
• Genes 
• Increased glomerular filtration rate
• Increased plasma prorenin activity 
• Increased sodium hydrogen and sodium lithium countertransport ,      Pregnancy  , underlying disease 

Pathophysiology

• Natural history of disease is complex 
• The courses of diabetic nephropathy is slow 
• They are included in 5 stage of renal involvement

Diagnosis

• The diagnosis is made upon the test results such as dipstick test or through ACR on 2 / more occasions over the period of 6 months 
• The false negative or false positive results may show up and they should be excluded.  
• The reason includes presence of confounding causes such as vigorous exercises,Urinary tract infections,Presence of blood in the urine 

Concentrates or diluted urine.

• Increased ACR in type 1 diabetes mellitus is due to diabetic kidney disease 
• 10-15% of people having type 2 diabetes has atypical appearance on renal biopsy 
• Presence of retinopathy makes kidney disease and glomerulosclerosis much more likely 
• Nephrosclerosis and tubulointerstitial changes are most commonly seen non-diabetic changes 

Pathology

• Kidney enlargement 
• Glomerular basement membrane increased thickness 
• In advanced stages,presence of large acellular nodules is seen

Hemodynamic changes 

• Increased glomerular capillary pressure
• Hyperfiltration along with nephropathy in type 1 diabetes mellitus

Hyperglycemia 

• Hyperglycemia leads to oxidative stress due to oxidation of protein kinase C , increased thrombosis, alterations in blood flow 
• Duration and severity of hyperglycemia are strong determinants of nephropathy

Albuminuria

• First clinical sign of albuminuria and with a gradual loss of glomerular filtration rate
• If albuminuria exceeds 10 mg/mmol,it is persistent and established nephropathy 

Blood pressure

• Increased are a  concomitant factor of nephropathy in type 1 patients may be more causative factor for type 2
• Drives nephropathy progression
• High risk of cardiovascular diseases 
• People with worse control over glycemia will have risk  of Nephropathy and retinopathy 
• Blood pressure of less than 130/80mmHg in patients with nephropathy is maintained
• In normotensive ,normoalbuminuric people with type 1 or 2 diabetes have no evidence to suggest antihypertensive pills that will prevent nephropathy 

Smoking

• Increases the risk in the patients with existing nephropathy ,compared with those without 
• Diet should be strictly followed in type 1 DM ,protein restriction can lowers the loss of glomerular filtration rate, albuminuria and mortality with established nephropathy

Treatment

• Patients with glomerular filtration rate less than 30 or with chronic kidney disease at stage 4, microscopic Hematuria,heavy proteinuria, underlying systemic disease or any suspected renal artery sclerosis are referred to the nephrologist as early as possible.
• Those with rate of progression that may develop End stage renal disease are referred for RRT .Because the survival rate is better 
• Stable condition with well controlled blood pressure and glycaemia required no referral

• Multifactorial interventions with the use of ACE inhibitors,Aspirin,lipid-lowering,smoking cessation,weight reduction, exercises and antioxidants therapy has been known to reduce cardiovascular morbidity and mortality in almost 80%of people with T2DM.
• Survival outcomes are better for those who receive renal transplantation .But less good chances. when compared ,for those with non diabetic renal disease 

II.Diabetic Retinopathy

• It is a complication of diabetes , resulting from damage to the smaller blood vessels ,generally after 10years of diabetes onset 
• It is a leading cause of blindness in adults of age Less than 65 years 
• Cataracts are more common in people with diabetes
• It is more prevalent in both type 1 and 2 diabetic patients
• After 15 years, more than 90%of people will have retinopathy and less than 60% will have proliferative Nephropathy
• After 20years ,around 99% will have retinopathy and 53% will have proliferative Nephropathy
• In more than 25% people with T2DM with retinopathy will be diagnosed within 2 years

Classification

1. R1 or Background retinopathy

• Microaneurysms 
• Hemorrhage
• Hard and soft exudates 

   2.R2 or Pre-proliferative retinopathy 

• Venous beading 
• Venous reduplications
• Intraretinal microvascular abnormalities
• Multiple blot hemorrhage 

    3.R3 or Proliferative nephropathy

• Pre retinal hemorrhage
• Neovascular glaucoma 
• New vessels over disc or everywhere    

   4.Maculopathy or ( M0 /M1)    

• Group is exudates within macula
• Microaneurysms
• Exudate ,retinal thickening within 1 disc diameter of centre of fovea 

      Pathology

• One of the main change is thickening of basement membrane and loss of pericytes forming acellular capillaries 
• Microaneurysms is the hallmark of retinal disease in diabetes 
• Smooth muscle cells death ,IRMA’s,impaired autoregulation are common features of retinopathy              

1.Background retinopathy 

• The earliest clinical feature is microaneurysms which seen as red dots 
• Intraretinal hemorrhage or blots are also present 
• Hard exudates and lipid deposits are also seen
• Cotton wool spots is a delay transmission along the nerve fibers caused due to ischemia
• Impact over vision is not present 

2.Pre proliferative retinopathy

• With increased ischemia,the retina shows increased number of blot hemorrhage
• Venous beading is a localized increased caliber of vein,whereas venous duplication is a dilation of pre pre-existing channel or Proliferation of a new channel.
• May impair vision

Factors indicative of progression are 4 quadrants of severe hemorrhage or 2 quadrants of IRMA or 1 quadrant with venous beading (4-2-1 rule) presence of any one of these factor has risk of 15% to proliferate in to retinopathy,if two the the chance of risk raises to 45-50% .

3.proliferative retinopathy

• New vessels develop  near of elsewhere in the optic disc or retina respectively
• The study reports that prompt Treatment with PRP or panretinal photocoagulation reduced the Visual loss by half or more 
• Vision already gets affected at this stage 

4.diabetic macular edema 

• Also called as maculopathy classified into diffuse ,focal, ischemic types 
• Focal maculopathy ,tends to form microaneurysms due to leakage 
• In diffuse type ,a generalized break down of blood -retinal barrier leading to vision loss
• In ischemia type enlarged foveal avascular zone is found 

 Clinical significant macular oedema

• Is defined as thickening of retina at /within 500 microns of the center of the macule  
• Focal retinal coag for CSMO 
• Vision loss is present 

Diagnosis 

• The diagnosis is made through urine albumin excretion rates 
• Random spot urine collection to measure albumin:creatinine ratio,24 hour urine collection
• Teleophthalmology is an new tool for diagnosis for direct eye examinations 

TREATMENT OPTIONS INCLUDES 

1.EYE SCREENING 

Those with type 1 &2 diabetes have their eyes screened during the period of diagnosis and at least every year thereafter 

2.when do we  refer  to expert 

Immediate referral

• Neovascular glaucoma
• Advance retinopathy
• Vitreous hemorrhage

Urgent referral 

• R3 

Routine referral 

• R2
• M1

Routine no Dr referral

•  Cataracts 

Other 

• R0/R1

• New screening techniques include Raman spectroscopy,Doppler flowmeter etc 
• Medical therapy includes Photocoagulation through laser 
• Surgical therapy includes panretinal photocoagulation for high risk individual and with macula edema 
• Vitrectomy for managing complications of diabetic retinopathy 

Conclusion 

• Regular screening and treatment by following the guidelines are highly recommended for further reduction in mortality and morbidity rates 

Frequently asked questions 

1.Does diabetic nephropathy cause retinopathy?

• No, diabetic nephropathy does  not cause retinopathy but patients will be diagnosed with type 2  diabetes could probably have any stage of microvascular complications such as retinopathy or nephropathy and even neuropathy 

2.Which comes first Diabetic retinopathy and nephropathy?

• These both complications are related together .The most common which comes first  out of two is diabetic retinopathy than nephropathy 

3.Can you have diabetic nephropathy without Retinopathy?

• As mentioned earlier the association between both these dreadful complications are organized .The nephropathy without Retinopathy is rare but retinopathy without nephropathy is common .
• This is because of the renal replacement therapies in diabetic nephropathy patients protected from retinopathy 

4.What is associated with neuropathy,nephropathy and retinopathy?

• Diabetic nephropathy is associated with proliferative Diabetic retinopathy,neuropathy and other cardiovascular diseases by univariate analysis
• In multivariate analysis,it is associated with proliferative Diabetic nephropathy and coronary artery disease

5.What happens in diabetic retinopathy?

• It is a complication of diabetes,caused by high blood glucose levels damaging the retina of the eye 
• It leads to other severe complications such as blindness,if left untreated 
• It usually takes several years to reach such dreadful complications for approximately around 10years.

6.Can diabetic retinopathy be corrected?

• Yes,it can be corrected with the treatment only to slow down the process or progression
• It cannot be cured 
• Even after the treatment done for the diabetic retinopathy the regular eye screening and check up is done to make sure for any recurrence

7.What are the symptoms of diabetic retinopathy?

• Spots 

• Fluctuations in vision 
• Dark areas in vision
• Blurred vision
• Vision loss 

8.How long does it take to develop diabetic nephropathy?

• Evidence suggests that it take around 2 to 5 years of diagnosis, in patients with type 1 diabetes mellitus to show up functional changes in kidney 

• Usually with in 10 to 25 years it may progress into more serious kidney diseases 

9.What are stages of diabetic nephropathy?

• Stage 1 : kidney damage present with normal kidney function and glomerular filtration rate of 90%or more 

• Stage 2 : kidney damage with loss (some) of function and GFR of 60-90% 
• Stage 3 : Mild to severe loss of function and Glomerular filtration rate of 30-60%
• Stage 4 : severe loss of kidney function and glomerular filtration rate of 15-30%

10.How is diabetic nephropathy diagnosed?

• To analysis protein in urine urinalysis is done
• Or imaging techniques includes x rays, ultrasound to access size and structure of kidneys 
• Other advanced imaging techniques include CT scans,MRI to determine the blood circulation in kidneys 
• Kidney biopsy can also be done