Overview of diabetic Overview of diabetic nephropathynephropathy

Overview of diabetic Overview of diabetic nephropathynephropathy

Dr. A. EmamiDr. A. Emami

Diabetic nephropathy occurs in Diabetic nephropathy occurs in

both type 1 and type 2 diabetes both type 1 and type 2 diabetes

mellitus, including diabetes due to mellitus, including diabetes due to

genetic defects of beta-cell genetic defects of beta-cell

function.function.

DN is the most important DN is the most important

disorder leading to RF in adult. disorder leading to RF in adult.

In the USA more than 44% of In the USA more than 44% of

patients entering RSP are diabetic.patients entering RSP are diabetic.

DX Clinical evidenceDX Clinical evidence

Staging of renal involvement in Staging of renal involvement in IDDMIDDM

Microalbuminuria:Microalbuminuria: Persistent excretion of Persistent excretion of Alb in the urine at rates that are above the Alb in the urine at rates that are above the normal range but below values detected normal range but below values detected by conventional methodsby conventional methods

2020μμg/min<UAE<200g/min<UAE<200μμg/ming/min

Persistent microalbuminuriaPersistent microalbuminuria

Urine should be steril in nonketotic Urine should be steril in nonketotic patients.patients.

Overt DNOvert DN

UAE 12-20UAE 12-20μμg/ming/min

Microalbuminuria has apredictive value of Microalbuminuria has apredictive value of approximately 75% to 80% for DN.approximately 75% to 80% for DN.

Type 1 diabetesType 1 diabetes

The epidemiology of diabetic nephropathy The epidemiology of diabetic nephropathy has been best studied in patients with type 1.has been best studied in patients with type 1.

Approximately Approximately 20 to 30 percent20 to 30 percent will have will have microalbuminuria microalbuminuria after a mean duration of after a mean duration of diabetes of diabetes of 15 years15 years . . Less than halfLess than half of these of these patients will progress to patients will progress to overt nephropathyovert nephropathy..

Microalbuminuria may regress or remain Microalbuminuria may regress or remain stable in a substantial proportion, probably stable in a substantial proportion, probably related to glycemic and blood pressure related to glycemic and blood pressure control.control.

Prior to the current period of Prior to the current period of

intensive monitoring and treatment, intensive monitoring and treatment,

it was suggested that 25 to 45 it was suggested that 25 to 45

percent of diabetic patients will percent of diabetic patients will

develop clinically evident diseasedevelop clinically evident disease

The overall The overall incidence of (ESRD)incidence of (ESRD) was also was also substantial, with reported rates of substantial, with reported rates of 4 to 174 to 17 percent at percent at 20 years from time of initial20 years from time of initial diagnosis and approximately 16 percent at diagnosis and approximately 16 percent at 30 years30 years ..

In comparison to these findings, In comparison to these findings, subsequent studies have found that the subsequent studies have found that the renal prognosis of type 1 diabetes, renal prognosis of type 1 diabetes, including the rate of progression to ESRD, including the rate of progression to ESRD, has dramatically improved over the last has dramatically improved over the last several decadesseveral decades

The onset of overt nephropathy in type The onset of overt nephropathy in type 1 diabetes is typically between 10 and 1 diabetes is typically between 10 and 15 years after the onset of the disease.15 years after the onset of the disease.

Those patients who have no proteinuria Those patients who have no proteinuria after 20 to 25 years have a risk of after 20 to 25 years have a risk of developing overt renal disease of only developing overt renal disease of only about 1 percent per year.about 1 percent per year.

Type 2 diabetesType 2 diabetesIn In Caucasians,Caucasians, the prevalence of progressive the prevalence of progressive

renal disease has generally been lower in renal disease has generally been lower in

type 2 diabetes than in type 1 diseasetype 2 diabetes than in type 1 disease . .

however, the use of modern therapies lowers however, the use of modern therapies lowers

the incidence of ESRD, even in groups at the incidence of ESRD, even in groups at

extremely high risk such as the extremely high risk such as the Pima IndiansPima Indians..

Data suggest that the renal risk Data suggest that the renal risk

is currently equivalent in the two is currently equivalent in the two

types of diabetestypes of diabetes..

With respect to the development and With respect to the development and progression of nephropathy among over progression of nephropathy among over 5000 type 2 diabetics enrolled in UKPDS, 5000 type 2 diabetics enrolled in UKPDS, the following results were reported; the following results were reported;

At ten years following diagnosis, the At ten years following diagnosis, the prevalence of prevalence of microalbuminuria,microalbuminuria, macroalbuminuriamacroalbuminuria, and either an , and either an elevated elevated plasma creatinineplasma creatinine concentration (defined concentration (defined asas 2.0 mg/dL) or requirement for renal 2.0 mg/dL) or requirement for renal replacement therapy was replacement therapy was 2525,, 5 5, and, and 0.80.8 percent, respectivelypercent, respectively. .

An estimation of the median time spent in each stage without progression to another nephropathy stage was 19, 11, and 10 years for those with no nephropathy, microalbuminuria, and macroalbuminuria, respectively.

Among those with an elevated plasma creatinine 2 mg/dL, renal replacement therapy was required after a median period of only 2.5 years.

RISKRISK FACTORSFACTORS

Studies in patients who have or Studies in patients who have or

do not have clinically evident diabetic do not have clinically evident diabetic

nephropathy have identified a nephropathy have identified a

number of factors as being number of factors as being

associated with increased risk of associated with increased risk of

renal involvement:renal involvement:

Genetic susceptibilityGenetic susceptibility — — Genetic Genetic susceptibility may be an important susceptibility may be an important determinant of both the determinant of both the incidence and incidence and severityseverity of diabetic nephropathy. of diabetic nephropathy.

The likelihood of developing diabetic The likelihood of developing diabetic nephropathy is markedly increased in nephropathy is markedly increased in patients with a diabetic patients with a diabetic sibling or sibling or parentparent who has diabetic nephropathy; who has diabetic nephropathy; these observations have been made in these observations have been made in both type 1 and type 2 diabetesboth type 1 and type 2 diabetes ..

AgeAge — — The impact of age at The impact of age at

onset of diabetes on the risk of onset of diabetes on the risk of

developing nephropathy and developing nephropathy and

ESRD is unclear. ESRD is unclear.

Blood pressureBlood pressure — — Prospective Prospective

studies have noted an association studies have noted an association

between the subsequent development between the subsequent development

of nephropathy and higher systemic of nephropathy and higher systemic

pressures.pressures.

Glomerular filtration rate Glomerular filtration rate —— • Approximately Approximately one-halfone-half of patients with of patients with

type 1type 1 diabetes of less than five years diabetes of less than five years duration have an elevated (GFR) that is duration have an elevated (GFR) that is 25 to 50 percent above normal.25 to 50 percent above normal.

• Those patients with glomerular Those patients with glomerular hyperfiltration appear to be at increased hyperfiltration appear to be at increased risk for DNrisk for DN .This is particularly true for .This is particularly true for overt nephropathy if the initial GFR is overt nephropathy if the initial GFR is above 150 mL/minabove 150 mL/min

The findings in type 2 diabetes are The findings in type 2 diabetes are somewhat differentsomewhat different. Up to . Up to 45 percent45 percent of of affected patients initially have a GFR that affected patients initially have a GFR that is more is more than 2 standard deviationsthan 2 standard deviations above above age-matched nondiabetic and obese age-matched nondiabetic and obese controls.controls. However, the degree of However, the degree of hyperfiltration (averaging hyperfiltration (averaging 117 to 133 117 to 133 mL/minmL/min) is less than that seen in type 1 ) is less than that seen in type 1 diabetics. Type 2 diabetics are also older diabetics. Type 2 diabetics are also older and more likely to have and more likely to have arteriosclerotic arteriosclerotic vascular diseasevascular disease which will limit increases which will limit increases in both glomerular filtration and in both glomerular filtration and glomerular sizeglomerular size

Glycemic controlGlycemic control ——

Diabetic nephropathy is more Diabetic nephropathy is more likely to develop in patients likely to develop in patients with worse glycemic control with worse glycemic control (higher HbA1c levels)(higher HbA1c levels)

RaceRace — — The incidence and severity of The incidence and severity of diabetic nephropathy are increased indiabetic nephropathy are increased in blacksblacks (3- to 6-fold compared to (3- to 6-fold compared to Caucasians), Caucasians), Mexican-AmericansMexican-Americans, and , and Pima IndiansPima Indians with type 2 diabetes with type 2 diabetes ..

• This observation in such genetically This observation in such genetically disparate populations suggests a primary disparate populations suggests a primary role for socioeconomic factors, such as role for socioeconomic factors, such as diet, poor control of hyperglycemia, diet, poor control of hyperglycemia, hypertension, and obesityhypertension, and obesity ..

ObesityObesity —— A high (BMI) has been associated A high (BMI) has been associated with an increased risk of CKD among with an increased risk of CKD among patients with diabetespatients with diabetes .In addition, weight .In addition, weight loss may reduce proteinuria and improve loss may reduce proteinuria and improve kidney function among patients with diabeteskidney function among patients with diabetes . .

Oral contraceptivesOral contraceptives —— An initial report An initial report suggested a link between oral contraceptive suggested a link between oral contraceptive use and the risk of diabetic nephropathy.use and the risk of diabetic nephropathy.

RELATION BETWEEN DIABETIC RELATION BETWEEN DIABETIC

NEPHROPATHY AND RETINOPATHYNEPHROPATHY AND RETINOPATHY

Based upon the correlation between Based upon the correlation between

retinopathy and nephropathy, the retinopathy and nephropathy, the 2007 2007

K/DOQI GuidelinesK/DOQI Guidelines for diabetes and chronic for diabetes and chronic

kidney disease suggest that;kidney disease suggest that;

chronic kidney disease should be attributed chronic kidney disease should be attributed

to diabetes in most patients with diabetes if to diabetes in most patients with diabetes if

microalbuminuria and diabetic retinopathy microalbuminuria and diabetic retinopathy

are both presentare both present. . By comparison, other By comparison, other

causes of CKD should be entertained if causes of CKD should be entertained if

diabetic retinopathy is absentdiabetic retinopathy is absent

OTHER RENAL DISEASESOTHER RENAL DISEASES — — Proteinuria in Proteinuria in

diabetes mellitus is occasionally due to a diabetes mellitus is occasionally due to a

glomerular disease other than DN. As glomerular disease other than DN. As

examples, membranous nephropathy, examples, membranous nephropathy,

minimal change disease, IgAN,HSP,TBM, and minimal change disease, IgAN,HSP,TBM, and

a proliferative GN have all been described.a proliferative GN have all been described.

The major clinical clues suggesting The major clinical clues suggesting

nondiabetic glomerular disease arenondiabetic glomerular disease are ::

Onset of proteinuria less than five years from Onset of proteinuria less than five years from the documented onset of diabetesthe documented onset of diabetes (since the (since the latent period for overt diabetic nephropathy latent period for overt diabetic nephropathy is usually at least 10 to 15 years); this is is usually at least 10 to 15 years); this is more difficult to ascertain in type 2 diabetics more difficult to ascertain in type 2 diabetics in whom the true onset of disease is not in whom the true onset of disease is not known.known.

The acute onset of renal disease: The acute onset of renal disease: Diabetic Diabetic nephropathy is a slowly progressive disorder nephropathy is a slowly progressive disorder characterized by increases in protein characterized by increases in protein excretion and the serum creatinine excretion and the serum creatinine concentration over a period of yearsconcentration over a period of years. .

Presence of an active urine sedimentPresence of an active urine sediment

containing red cells (particularly containing red cells (particularly

acanthocytes) and cellular casts. Patients acanthocytes) and cellular casts. Patients

with only microscopic hematuria may have with only microscopic hematuria may have

TBM disease, which may affect up to nine TBM disease, which may affect up to nine

percent of the general population, with or percent of the general population, with or

without underlying diabetic nephropathywithout underlying diabetic nephropathy

In type 1 diabetes, the absence of diabetic In type 1 diabetes, the absence of diabetic

retinopathy or neuropathy. retinopathy or neuropathy.

In contrast, lack of retinopathy in In contrast, lack of retinopathy in

type 2 diabetes does not preclude type 2 diabetes does not preclude

diabetic nephropathy, which diabetic nephropathy, which

remains the most likely diagnosisremains the most likely diagnosis

Signs and/or symptoms of other systemic Signs and/or symptoms of other systemic disease.disease.

Significant reduction in the glomerular Significant reduction in the glomerular filtration ratefiltration rate (>30 percent) within two to (>30 percent) within two to three months of the administration of ACE three months of the administration of ACE inhibitors or angiotensin II receptor inhibitors or angiotensin II receptor blockers.blockers.

Treatment and Treatment and prevention of prevention of diabetic diabetic nephropathynephropathy

IMPORTANCE OF GLYCEMIC CONTROLIMPORTANCE OF GLYCEMIC CONTROL ——

The efficacy of strict glycemic control The efficacy of strict glycemic control

depends in part upon the stage at which it is depends in part upon the stage at which it is

begun and the degree of normalization of begun and the degree of normalization of

glucose metabolism;glucose metabolism;

intensive insulin therapy has the following intensive insulin therapy has the following

benefits with respect to the kidney;benefits with respect to the kidney;

It can partially reverse the glomerular It can partially reverse the glomerular

hypertrophy and hyperfiltrationhypertrophy and hyperfiltration

It can delay the development of It can delay the development of

microalbuminuria.microalbuminuria.

It can stabilize or decrease protein It can stabilize or decrease protein

excretion in patients with excretion in patients with

microalbuminuria, although this microalbuminuria, although this

effect may not be apparent until effect may not be apparent until

relative normoglycemia has been relative normoglycemia has been

maintained for two years. maintained for two years.

Blood pressure controlBlood pressure control —— Strict blood pressure Strict blood pressure

control is clearly important for preventing control is clearly important for preventing progression of diabetic nephropathy and other progression of diabetic nephropathy and other complications, however the complications, however the optimal lower limit for optimal lower limit for systolic blood pressure is unclear.systolic blood pressure is unclear.

In the United Kingdom Prospective Diabetes Study In the United Kingdom Prospective Diabetes Study (UKPDS), each 10 mmHg reduction in systolic (UKPDS), each 10 mmHg reduction in systolic pressure was associated with a 12 percent risk pressure was associated with a 12 percent risk reduction in diabetic complicationsreduction in diabetic complications (P<0.001); the (P<0.001); the lowest risk occurred at a systolic pressure below lowest risk occurred at a systolic pressure below 120 mmHg120 mmHg

There is now clear evidence that There is now clear evidence that antihypertensive therapy (particularly with an antihypertensive therapy (particularly with an ACE inhibitorACE inhibitor) can reduce the rate of ) can reduce the rate of progression in patients with progression in patients with type 1type 1 diabetes diabetes and overt nephropathyand overt nephropathy..

In patients with In patients with type 2type 2 diabetes, more data diabetes, more data are currently available on the preferential are currently available on the preferential renoprotective efficacy of angiotensin renoprotective efficacy of angiotensin receptor blockers receptor blockers (ARBs).(ARBs). However, ACE However, ACE inhibitors appear to have a similar benefitinhibitors appear to have a similar benefit..

Other antihypertensivesOther antihypertensives — — Most Most

sympathetic blockers and sympathetic blockers and

dihydropyridine CCB do not have dihydropyridine CCB do not have

significant antiproteinuric action significant antiproteinuric action

despite effective blood pressure despite effective blood pressure

reduction, unlike nondihydropyridine reduction, unlike nondihydropyridine

CCB.CCB.

Although the dihydropyridine CCB Although the dihydropyridine CCB

(such as(such as nifedipinenifedipine, , nitrendipine, nitrendipine,

andand amlodipineamlodipine)) may be effective in may be effective in

lowering BP, they have a variable lowering BP, they have a variable

effect ranging from increased effect ranging from increased

protein excretion to no effect to a protein excretion to no effect to a

fall in protein excretion in different fall in protein excretion in different

studies.studies.

Only Only diltiazemdiltiazem andand verapamilverapamil appear to be as consistently appear to be as consistently effective aseffective as an an ACE ACE inhibitor or inhibitor or ARBARB in lowering protein excretion in lowering protein excretion in diabetic patientsin diabetic patients; ; furthermore, furthermore, the antiproteinuric effects of the antiproteinuric effects of verapamil and an ACE inhibitor verapamil and an ACE inhibitor may be may be additiveadditive ..

patients on ACE inhibitors or ARBs patients on ACE inhibitors or ARBs who do not have sufficient reduction who do not have sufficient reduction in proteinuria despite appropriate in proteinuria despite appropriate blood pressure goals should be blood pressure goals should be instructed to take a low sodium diet.instructed to take a low sodium diet. An assessment of baseline sodium An assessment of baseline sodium intake can be undertaken by obtaining intake can be undertaken by obtaining a 24-hour urine for sodium and a 24-hour urine for sodium and creatinine.creatinine.

Aldosterone antagonismAldosterone antagonism — — Diuretics have Diuretics have generally not been considered to have an generally not been considered to have an antiproteinuric effect despite reductions in antiproteinuric effect despite reductions in blood pressureblood pressure. . However, aldosterone However, aldosterone antagonists appear to reduce proteinuria antagonists appear to reduce proteinuria when used alonewhen used alone, , and to have an and to have an additive additive effect on proteinuria when used in effect on proteinuria when used in combination with an combination with an ACE inhibitor or an ARBACE inhibitor or an ARB in both type 1 and type 2 diabetes.in both type 1 and type 2 diabetes. Further blood pressure reduction may Further blood pressure reduction may partially explain the beneficial effect, partially explain the beneficial effect, although an although an anti-inflammatory mechanismanti-inflammatory mechanism has also been proposedhas also been proposed

There are no long term data regarding benefit with There are no long term data regarding benefit with the combination of ACE inhibitor or ARB and the combination of ACE inhibitor or ARB and aldosterone blockade in terms of slowing the rate of aldosterone blockade in terms of slowing the rate of loss of GFRloss of GFR. The risk of inducing or aggravating . The risk of inducing or aggravating hyperkalemia in patients with long-standing diabetic hyperkalemia in patients with long-standing diabetic nephropathy may limit the use of aldosterone nephropathy may limit the use of aldosterone antagonistsantagonists..

However, aldosterone blockade in combination with However, aldosterone blockade in combination with an ACE inhibitor or ARB is indicated in the therapy an ACE inhibitor or ARB is indicated in the therapy of of heart failureheart failure. Close monitoring for the . Close monitoring for the development of hyperkalemia is required in patients development of hyperkalemia is required in patients with diabetic nephropathywith diabetic nephropathy. .

ACE inhibitorsACE inhibitors, , ARBsARBs, , diltiazem, , andand verapamil have have relatively unique beneficial effects on proteinuriarelatively unique beneficial effects on proteinuria

The reduction in protein excretion may reflect both The reduction in protein excretion may reflect both a fall in intraglomerular pressure and, at least with a fall in intraglomerular pressure and, at least with the ACE inhibitors, an apparent direct improvement the ACE inhibitors, an apparent direct improvement in the size-selective properties of the GBM .(via an in the size-selective properties of the GBM .(via an uncertain mechanism)uncertain mechanism)

The observation that protein excretion progressively The observation that protein excretion progressively declines over time is consistent with an effect on declines over time is consistent with an effect on permselectivity, since the hemodynamic effects of permselectivity, since the hemodynamic effects of ACE inhibition occur very rapidly and are then stableACE inhibition occur very rapidly and are then stable

PRESERVATION OF RENAL PRESERVATION OF RENAL FUNCTIONFUNCTION

Protein restrictionProtein restriction — — It remains uncertain It remains uncertain whether dietary protein restriction slows whether dietary protein restriction slows the long-term decline in GFR in DN. Two the long-term decline in GFR in DN. Two small controlled trials (35 and 19 patients, small controlled trials (35 and 19 patients, respectively) demonstrated that protein respectively) demonstrated that protein (and phosphate) restriction (0.6 g/kg per (and phosphate) restriction (0.6 g/kg per day) slowed the rate of decline in GFR by day) slowed the rate of decline in GFR by 60 to 75 percent from, for example, 60 to 75 percent from, for example, approximately 12 mL/min per year to 3 approximately 12 mL/min per year to 3 mL/min per yearmL/min per year

WEIGHT REDUCTIONWEIGHT REDUCTION — — Marked Marked

decreases in proteinuria may be decreases in proteinuria may be

observed in obese diabetics who observed in obese diabetics who

lose weight.lose weight.

HYPERLIPIDEMIAHYPERLIPIDEMIA — — Hyperlipidemia is Hyperlipidemia is common in diabetic patients, a tendency common in diabetic patients, a tendency that is increased by the development of that is increased by the development of renal insufficiency. Aggressive lipid renal insufficiency. Aggressive lipid lowering is an important part of the lowering is an important part of the medical management of all diabetic medical management of all diabetic

patients, patients, since diabetes is considered since diabetes is considered a coronary heart disease equivalent.a coronary heart disease equivalent.

In addition to promoting systemic In addition to promoting systemic

atherosclerosis, an elevation in lipid atherosclerosis, an elevation in lipid

levels also may contribute to the levels also may contribute to the

development of glomerulosclerosis development of glomerulosclerosis

in chronic kidney diseasein chronic kidney disease. .

Other agentsOther agents — — A variety of other A variety of other

agents have been tried with the goal of agents have been tried with the goal of

reduction of proteinuria in diabetes and reduction of proteinuria in diabetes and

other proteinuric nephropathies. As an other proteinuric nephropathies. As an

exampleexample, , pentoxifylline appears to appears to

block tubulointerstitial fibrosisblock tubulointerstitial fibrosis in in

experimental models.experimental models.

Thus, an aggressive Thus, an aggressive

combined approach may combined approach may

offer optimal protection offer optimal protection

against disease progression against disease progression

for patients with either type 1 for patients with either type 1

and type 2 diseaseand type 2 disease

RECOMMENDATIONSRECOMMENDATIONSIt now seems clear in It now seems clear in type 1type 1 diabetes that diabetes that ACEIACEI, as , as part of a therapeutic regimen to achieve part of a therapeutic regimen to achieve BP goalsBP goals, , both both lower protein excretionlower protein excretion and and slow the rate of slow the rate of disease progressiondisease progression in patients with in patients with microalbuminuria and in those with overt microalbuminuria and in those with overt nephropathynephropathy . .

a similar effect is seen in type 2 diabetes with ARBs a similar effect is seen in type 2 diabetes with ARBs or ACE inhibitors.or ACE inhibitors.

It is important to appreciate, however, that these It is important to appreciate, however, that these agents slow the rate of progression, but do not stop agents slow the rate of progression, but do not stop progression andThus, other modalities are also progression andThus, other modalities are also requiredrequired

ACE inhibitors and ARBs appear to provide ACE inhibitors and ARBs appear to provide equivalent renal protection in patients with equivalent renal protection in patients with type 2 diabetes and microalbuminuria. type 2 diabetes and microalbuminuria.

This equivalence is less clear among those This equivalence is less clear among those with overt proteinuriawith overt proteinuria, as renal protection is , as renal protection is better studied with ARBs in this setting. better studied with ARBs in this setting. Despite this theoretical limitation, Despite this theoretical limitation, we we suggest either an ARB or an ACE inhibitor suggest either an ARB or an ACE inhibitor (if tolerated) for the prevention of (if tolerated) for the prevention of progression of nephropathy in patients with progression of nephropathy in patients with type 2 diabetestype 2 diabetes. .

Compared to monotherapy with an Compared to monotherapy with an

ACE inhibitor or ARB alone, ACE inhibitor or ARB alone,

combined therapy produced a combined therapy produced a

greater reduction in protein greater reduction in protein

excretion in most studies, and as excretion in most studies, and as

demonstrated in nondiabetic demonstrated in nondiabetic

chronic renal failure, a greater chronic renal failure, a greater

degree of slowing of progressiondegree of slowing of progression

Type 1 diabetesType 1 diabetes — — Patients with Patients with type 1type 1 diabetes diabetes should probably be should probably be screened yearlyscreened yearly (after the first (after the first five yearsfive years) for the presence of microalbuminuria.) for the presence of microalbuminuria.

Use of the Use of the albumin-to-creatinine ratioalbumin-to-creatinine ratio in an untimed in an untimed urinary sample is recommended as the urinary sample is recommended as the preferredpreferred screening strategy for all diabetic patientsscreening strategy for all diabetic patients

Measurement of the serum creatinine concentration Measurement of the serum creatinine concentration and estimation of the GFR should also be performed.and estimation of the GFR should also be performed.

An elevated albumin-to-creatinine ratio should be An elevated albumin-to-creatinine ratio should be confirmed with at least two additional tests confirmed with at least two additional tests performed over the subsequent 3 to 6 months, with performed over the subsequent 3 to 6 months, with confirmation of the diagnosis requiring at least 2 of 3 confirmation of the diagnosis requiring at least 2 of 3 positive samplespositive samples

Type 2 diabetesType 2 diabetes — — Screening for Screening for

microalbuminuria is not as useful in microalbuminuria is not as useful in

type 2 diabetes because it is not as type 2 diabetes because it is not as

predictive of progression to overt predictive of progression to overt

nephropathy as in type 1 diabetes.nephropathy as in type 1 diabetes.

Recommendations :Recommendations :The following recommendations for The following recommendations for therapeutic goals are consistent with the therapeutic goals are consistent with the K/DOQIK/DOQI Clinical Practice Guidelines for Clinical Practice Guidelines for diabetes and chronic kidney disease;diabetes and chronic kidney disease;

A reduction in protein excretion to less than A reduction in protein excretion to less than 500 to 1000 mg/day; recognizing the difficulty 500 to 1000 mg/day; recognizing the difficulty of achieving such a goal in many patients, of achieving such a goal in many patients, we recommend a minimum reduction of at we recommend a minimum reduction of at least 60 percent of baseline valuesleast 60 percent of baseline values

A reduction in blood pressure to less A reduction in blood pressure to less than 130/80 mmHg. than 130/80 mmHg.

      Caution:Caution: The diastolic blood The diastolic blood pressure should not be lowered below pressure should not be lowered below 75 mmHg in patients with active 75 mmHg in patients with active coronary disease, and the systolic coronary disease, and the systolic blood pressure should not be lowered blood pressure should not be lowered to below 110 mmHg in any patientto below 110 mmHg in any patient..

Monitoring in patients with DMMonitoring in patients with DM

Smoking cessation every visitSmoking cessation every visitBP control every visitBP control every visitDilated eye exam annuallyDilated eye exam annuallyFoot examination annually Foot examination annually Serum lipid profile annuallySerum lipid profile annuallyHbA1c every 3 to 6 monthHbA1c every 3 to 6 monthMicroalbuminuria annuallyMicroalbuminuria annuallySerum Cr As indicated.Serum Cr As indicated.ECG annuallyECG annually

Pneumovax vaccination one timePneumovax vaccination one timeInfluanza vaccination annuallyInfluanza vaccination annually

Dialysis in diabetic nephropathyDialysis in diabetic nephropathy

Diabetes is the most common cause of Diabetes is the most common cause of new patients requiring renal new patients requiring renal replacement therapy, accounting for replacement therapy, accounting for approximately approximately 46 percent of cases in 46 percent of cases in the United Statesthe United States.. Although less Although less frequent in other countries, frequent in other countries, 34 and 3034 and 30 percent of incident dialysis patients percent of incident dialysis patients have diabetes in have diabetes in Germany and Germany and Australia,Australia, respectively respectively ..

PATIENT SURVIVALPATIENT SURVIVAL —— Patient survivalPatient survival in in diabetics on maintenance dialysis is diabetics on maintenance dialysis is lowerlower than that seen in nondiabetics with ESRD than that seen in nondiabetics with ESRD due to chronic glomerular disease or due to chronic glomerular disease or hypertensionhypertension . .

only approximately 25 percent of patients only approximately 25 percent of patients with diabetes survived five years after with diabetes survived five years after initiation of dialysis.initiation of dialysis.Survival also varies Survival also varies inversely with age, being best in young inversely with age, being best in young patients with good blood pressure control patients with good blood pressure control and no clinically evident cardiac diseaseand no clinically evident cardiac disease

Cardiovascular disease is the most Cardiovascular disease is the most

common cause of death, accounting common cause of death, accounting

for more than one-half of casesfor more than one-half of cases ..

the tissue deposition of advanced the tissue deposition of advanced

glycosylation end products glycosylation end products (AGEs)(AGEs)

may also enhance cardiovascular may also enhance cardiovascular

mortality once dialysis is begun.mortality once dialysis is begun.

DIALYSIS VERSUS RENAL DIALYSIS VERSUS RENAL

TRANSPLANTATIONTRANSPLANTATION ::

In one USRDS report relating to In one USRDS report relating to

diabetics with end-stage renal disease, diabetics with end-stage renal disease,

patient survival at five years after renal patient survival at five years after renal

transplantation in diabetics ranged from transplantation in diabetics ranged from

75 to 83 percent at five years75 to 83 percent at five years

HEMODIALYSIS VERSUS PERITONEAL DIALYSISHEMODIALYSIS VERSUS PERITONEAL DIALYSIS — —

Choice of a dialysis modality in diabetics is Choice of a dialysis modality in diabetics is

dependent in part upon the following factors which dependent in part upon the following factors which

apply to nondiabetics as wellapply to nondiabetics as well..

Comorbid conditionsComorbid conditions

Home situationHome situation

Ability to tolerate volume shifts —Ability to tolerate volume shifts — Diabetic patients Diabetic patients

with autonomic neuropathy are often more likely to with autonomic neuropathy are often more likely to

have hypotensive episodes during hemodialysis.have hypotensive episodes during hemodialysis.

Fluid removal is more gradual with CAPD and Fluid removal is more gradual with CAPD and

therefore hypotension is not a problem unless the therefore hypotension is not a problem unless the

patient becomes volume depletedpatient becomes volume depleted. .

Status of the vasculature and/or Status of the vasculature and/or abdomen —abdomen — Older patients with type 2 Older patients with type 2 diabetes are more likely to have severe diabetes are more likely to have severe peripheral vascular disease that limits peripheral vascular disease that limits the ability to create and sustain the ability to create and sustain adequate vascular access for adequate vascular access for hemodialysis. Unfortunately, these are hemodialysis. Unfortunately, these are often the same patients who are unable often the same patients who are unable to perform CAPD due to concomitant to perform CAPD due to concomitant illnessesillnesses. . Risk and history of infectionRisk and history of infection

RECOMMENDATIONSRECOMMENDATIONS

The following are our recommendations concerning The following are our recommendations concerning renal replacement therapy in dialysis patientsrenal replacement therapy in dialysis patients::

Renal and renal-pancreas transplantation should be Renal and renal-pancreas transplantation should be offered to any suitable diabetic patient with end-offered to any suitable diabetic patient with end-stage renal diseasestage renal disease

For those requiring dialysis, we continue to For those requiring dialysis, we continue to recommend peritoneal dialysis to diabetics who recommend peritoneal dialysis to diabetics who have adequate manual dexterity and visual acuity to have adequate manual dexterity and visual acuity to perform this technique, although there is no perform this technique, although there is no consensus to support this recommendation; very consensus to support this recommendation; very few such patients opt for home hemodialysis which few such patients opt for home hemodialysis which is associated with the highest survival ratesis associated with the highest survival rates

Given the problems with hemodialysis Given the problems with hemodialysis access due to vascular disease, early and access due to vascular disease, early and close attention must be paid to the close attention must be paid to the development of the vascular access in development of the vascular access in diabetic patients with chronic renal disease. diabetic patients with chronic renal disease. As with nondiabetics, the preferred type is As with nondiabetics, the preferred type is a native arteriovenous fistulaThe optimal a native arteriovenous fistulaThe optimal dose of peritoneal dialysis or hemodialysis dose of peritoneal dialysis or hemodialysis in diabetic patients is uncertain. We aim for in diabetic patients is uncertain. We aim for the same goals in diabetics as in the same goals in diabetics as in nondiabeticsnondiabetics

Most studies, after adjustment for Most studies, after adjustment for

comorbid factors, have not found a comorbid factors, have not found a

statistically significant survival statistically significant survival

difference between hemodialysis difference between hemodialysis

and CAPD in diabetic patientsand CAPD in diabetic patients ..