Dr.

Erna Fitrisia SpPD

 Jumlah pasien DM terus bertambah dan
merupakan penyebab tersering PGK.
Nefropathy Diabetik terjadi pada sekitar 20
40 % pasien DM
Tujuan utama adalah pengendalian kadar
gula darah
Pemberian terapi DM memerlukan berbagai
pertimbangan terkait perubahan
farmakokinetik pada PGK
 Pengendalian kadar gula darah sangat
penting untuk memperlambat atau mencegah
terjadinya penyakit ginjal pada DM
Ada banyak jenis OAD tetapi hanya sebagian
kecil yang aman dan banyak OAD yang
memerlukan penyesuaian dosis.
Target ideal HbA1c sekitar 7% tetapi target
ini disesuaikan dengan kebutuhan pasien.
 The 2007 Kidney Disease Outcomes Quality
Initiative (KDOQI) guidelines for Diabetes and
CKD endorse a target A1c of <7.0 % but their
updated 2012 guidelines instead recommend
an A1c of ~7.0 %.
HbA1c diperiksa 4 kali dalam 1 tahun
untuk menilai kontrol glikemik pasien
 Nondialysis CKD patients For most
predialysis CKD patients, we suggest using an
HbA1c target of approximately 7 percent,
although the risks and benefits of targeting this
goal are uncertain

K/DOQI and KDIGO : patients who are at risk for

hypoglycemia should not be treated to an HbA1c
<7 percent and that the target HbA1c may be
higher than 7 percent in individuals who have
comorbidities or limited life expectancy and who
are at risk for hypoglycemia
 Dialysispatients
HbA1c goal of 7 to 8 percent
For patients who are relatively young (<50
years) and without significant comorbid
conditions, target an HbA1c goal that is close
to 7 percent (ie, 7 to 7.5).
Among older patients with multiple comorbid
conditions, the HbA1c target is closer to 8
percent (ie, 7.5 to 8).
 The nonpharmacologic therapies
dietary modification,exercise, and weight
reduction. The additional burden of CKD
dietary requirements (for example salt,
protein, and volume restrictions) may further
complicate diets in patients with diabetes
Pharmacologic therapies include insulin and
oral agents
 the choice of initial agent depends upon :
-glycemic goals
- the risk of medication-associated adverse events
(hypoglycemia, lactic acidosis)
-patient preferences and convenience.
may be treated with an oral agent, although many patients
end up on insulin therapy because it is more effective.
The oral agents that are thought to be relatively safe in
patients with nondialysis CKD. If an oral agent is used, the
short-acting sulfonylurea, glipizide, is the preferred agent
among nondialysis CKD patients who have an estimated
glomerular filtration rate (eGFR) <30 mL/min/1.73. The
dose for glipizide is 2.5 to 10 mg/day.
long-acting sulfonylureas are generally not recommended
in any CKD patient with type 2 diabetes, because of the
risk of hypoglycemia.
 The 2012 Kidney Disease Outcomes Quality
Initiative (K/DOQI) guidelines : metformin
may be used among patients with an eGFR
>45 mL/min/1.73 .
Other agents including thiazolidinediones,
alpha-glucosidase inhibitors, and dipeptidyl
peptidase-4 (DPP-4) inhibitors are generally
not considered first-line agents among CKD
patients, because of limited data regarding
long-term safety and efficacy.
Sitagliptin and Saxagliptin require dose
adjustment in the setting of reduced GFR.
 Patients who fail therapy with oral agents are treated with
insulin. The indications for initiating insulin therapy and
the principles underlying insulin therapy are the same for
nondialysis CKD patients as for the general diabetic
population.
The starting dose of insulin may need to be lower than
would ordinarily be used for patients with normal kidney
function. CKD is associated with decreased renal and
ultimately hepatic metabolism of insulin
No dose adjustment is required if the GFR is >50 mL/min
The insulin dose should be reduced to approximately 75
percent of baseline when the GFR is between 10 and
50 mL/min
The dose should be reduced by as much as 50 percent
when the GFR is <10 mL/min
 2005 K/DOQI guidelines:among dialysis patients,
newer insulin regimens and insulin preparations
should be used rather than oral agents for
glycemic control.
The principles of insulin therapy are the same
for dialysis patients as for the general diabetic
population.
The initial dose of insulin should be decreased by
approximately 50 percent. The dose should be
titrated upward, as indicated by blood glucose
monitoring.
Some suggest that long-acting insulin
preparations should be avoided, while others
feel that such agents should be used.
 Some clinicians prefer to use oral agents rather
than insulin, especially among patients who are
already on these agents and have achieved
acceptable glycemic control. The preferred
agents are glipizide or repaglinide since they are
primarily metabolized by the liver, since inactive
or only very weakly active metabolites are
excreted in the urine, and since the risk of
hypoglycemia is lower than with other oral
agents.
Dose reductions are not necessary
 In general, a large number of oral agents are
available to manage type 2 diabetes mellitus.
Knowledge of the metabolism of these agents
in patients with kidney dysfunction is
essential, given that significant toxicity,
including prolonged hypoglycemia, can be
associated with some of the drugs
 Glyburide has weak active metabolites that
are excreted in the urine and accumulate in
patients with impaired kidney function.
Glimepiride is primarily metabolized by the
liver, with renal excretion of active
metabolites
Glipizide and tolbutamide are metabolized
by the liver and primarily excreted in the
urine as inactive metabolites.
 Repaglinide or nateglinide, are sulfonylurea-like agents that
stimulate insulin secretion
Repaglinide is principally metabolized by the liver, with less than
10 percent renally excreted.
Maintenance doses were lower in patients with advanced CKD. In
patients with an eGFR between 20 and 40 mL/min, initiation of
treatment should be with 0.5 mg before the largest meal and
then advanced to 0.5 mg prior to other meals, as needed.
Close, careful monitoring of blood glucose levels is essential as
the dose is titrated. In patients with an eGFR of 40 mL/min, no
dose adjustment is necessary, and repaglinide can be initiated at
0.5 mg prior to each meal with dose titration based upon blood
glucose levels. Repaglinide has not been studied in patients with
an eGFR of <20 mL/min.
Nateglinide is hepatically metabolized, with renal excretion of
active metabolites. With decreased kidney function, the
accumulation of active metabolites and hypoglycemia has
occurred. This drug must therefore be used cautiously in this
setting, if at all.
 Although some DPP-4 inhibitors have been studied in
patients with kidney dysfunction, the data are limited
Therefore, we suggest not using DPP-4 inhibitors among
such patients.
Dose adjustments are needed for some agents in this class.
Linagliptin is only minimally excreted in the urine (<10
percent) and does not require dose adjustment in patients
on dialysis, but its use in ESRD patients is limited.
Sitagliptin is largely excreted in the urine, with 70 to 80
percent of an oral dose appearing unchanged in the urine.
If sitagliptin is used among ESRD patients, a dose reduction
to 25 mg daily (usual dose 100 mg daily) is recommended.
Saxagliptin and its primary active metabolite are excreted
in the urine (total urinary excretion approximately 60 to 75
percent); a daily dose of 2.5 mg is the recommended dose
for patients with ESRD. Saxagliptin is removed by
hemodialysis and should be administered after dialysis.
 Rosiglitazon,Pioglitazone should be avoided
in patients with advanced CKD, especially
those with preexisting heart failure, given
the risk of edema and heart failure.
 Acarbose atau miglitol
are not recommended in patients with renal
dysfunction
 Metformin , are primarily excreted
unchanged in the urine.
Thus, patients with kidney dysfunction are
more susceptible to drug accumulation and
lactic acidosis with these compounds.
They should therefore be avoided in patients
with severe CKD
 Hyperglycemia
- Inadequate insulin dose and noncompliance (with diet or
the insulin regimen) are the most common causes of
persistent hyperglycemia in diabetic dialysis patients
(defined as an HbA1c level >9 percent)
- The approach to these issues is the same for chronic
kidney disease (CKD) patients as for non-CKD patients
Severe hyperglycemia and ketoacidosis
Severe hyperglycemia, with serum glucose concentrations
occasionally >1000 mg/dL (55 mmol/L)
Unlike those without end-stage renal disease (ESRD),
however, hypovolemia and marked hypernatremia do not
occur, since glucosuria is absent in anuric individuals.
The net effect is minimal symptoms, even among those
with extreme hyperglycemia
However, these patients may have marked hyperkalemia
,hyponatremia and acute intravascular volume expansion
 Instead of fluid replacement, management is principally dependent upon
the administration of low doses of intravenous insulin (commonly
beginning at a dose of 2units/hour)
As with nondialysis patients with severe hyperglycemia and diabetic
ketoacidosis, serum glucose and potassium concentrations must be
closely monitored.
Hypoglycemia
Frequent or persistent hypoglycemia in diabetic dialysis patients is often
due to severe underdialysis, with poor calorie intake, or occult disease,
such as infection or malignancy. Frequent adjustment of insulin dose and
evaluation of blood glucose diaries are essential in this setting, as is
provision of an adequate dialysis dose
Drugs that interfere with the counterregulatory response to hypoglycemia
(such as beta blockers) and long-acting insulin and oral agents should be
discontinued, if possible, until more stable glycemic control without
hypoglycemia is achieved.
Alternating hypoglycemia and hyperglycemia
ESRD patients with diabetes often have gastroparesis, which complicates
the timing of insulin injections. Gastric-emptying studies will confirm the
diagnosis, which can often be effectively treated with metoclopramide.
Improvement in glycemic control may also improve gastric motility.
 Other causes of brittle blood glucose include
-patient misunderstanding of the timing of
insulin injections
-poor compliance with dietary restrictions and
insulin therapy
-erratic eating habits
-poor timing of continuous ambulatory peritoneal
dialysis (CAPD) exchanges
These problems can often be corrected with
patient re-education.
Noncompliance, impaired vision, and a
depressive illness should also be sought.
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