About 25% of Type 1DM's have a GFR exceeding the upper limit of normal at diagnosis. As the above shows (solid line) the frequency distribution of the GFR in these patients seems shifted to the right. With good control the GFR returns to normal over a period of several months

The cumulative incidence of clinical proteinuria in Type 1 DM patients according to duration of diabetes and calendar year of diagnosis. This data published by Krolewski in 1987 has been replicated by others more recently. However overall number of diabetics on dialysis is increasing because of Type 2 DM's Particular ethnic groups (Asian and Afro-Caribbean) seem more vulnerable

Diabetic nephropathy and retinopathy go together
This is a very close relationship in type 1 diabetes, less so in type 2 diabetes. In Type 2 DM some investigators have reported upto 20% of patients with proteinuria have a non diabetic cause for their proteinuria irrespective of the retinal findings. This depends on many things including selection criteria for biopsy and pre-biopsy risk factors for other diseases.

Not all diabetics get nephropathy ~35%
Genetic factors are important in some populations such as Pima Indians where 200 of a tribe of 8000 are on dialysis Concordance for diabetic nephropathy appears increased in Twins Hypertension pre-existing the diabetes has by some worker to be a risk factor Raised GFR at onset appears to be a risk factor nephropathy Glycemic control is a factor as suggested by the UKPDS and the DCCT studies possibly through AGE products

Diabetic Nephropathy
Routine dipsticks detect overt proteinuria, this correlates to about 0.5 gm of proteinuria per day. Normal kidneys excrete up to 30 mg per day Microalbuminuria is 30 to 300 mg per day or 20 to 200 ug per min. Urinary protein excretion rates increase with exercise and fevers Infection needs to be excluded as a cause of proteinuria. A single measurement of microalbuminuria has a positive predictive value of 0.6 for the development of overt proteinuria. Therefore single values should be repeated. Special urine dipsticks, time urine collections or urine albumin creatinine ratios can be used to detect Microalbuminuria. The development of proteinuria is closely associated with the development of hypertension.

DCCT & UKPDS studies
Glycaemic control may help Particularly in the early phase Strict blood pressure control is beneficial After 3 years of therapy 30% of patients are on 3 antihypertensives

130/80 or better is probably the target for a proteinuric diabetic. Some groups are suggesting those with proteinuria over 1gm/day should have a target of 120/75. ACE inhibitors first choice in Type 1 DM and where renovascular disease thought to be unlikely. Calcium Channel Blocker's first choice in Afro-Caribbean patients who have low renin states The UKPDS study found ACE inhibitors and B blockers to be equally effective.

Mortality of proteinuria

Relative mortality of insulin-dependent diabetics with (upper curves) and without (lower curves) clinical proteinuria as function of age (Dashed lines women, solid lines, men) Whatever the cause of death by age of 45 in proteinuric Type 1 DM's mortality is 20-40 times higher than non proteinuric Type 1 DM's and they themselves are twice the normal population.

Prognosis on Renal replacement therapy
The mean time from onset of diabetes to RRT is approx 17/18 years. Is often difficult to determine the date of onset of diabetes in Type 2 DM but where it has been determined the time to RRT is thought to be very similar to Type 1 DM.

The five year survival remains at about 25%. The percentage with transplants increases with time, this is selection phenomenon as those patients able to receive a transplant live longer.

Problems on Dialysis
Eyes and anticoagulation

CVS instability on dialysis

Gustatory sweating

GI autonomic neuropathy

Drugs in Diabetics with Renal Failure
Insulin has a molecular weight of around 6,000 25% metabolised by the kidney, as renal failure progresses the patients need less insulin or tablets. Metformin can cause lactic acidosis and should be used with caution in patients with liver or renal disease. Oral agents need to be adjusted for the level of renal function and the short acting agents are to be preferred. Eg gliclazide, Tobutamide The place of glitazones in renal impairment is presently uncertain.