Pengukuan Tekanan Darah

Sumber : Bates Guide to Physical Examination

Pemilihan Manset Tekanan Darah yang Tepat :

-

Lebar kantong manset yang dapat dikembungkan harus berukuran kira-kira 40% lingkar
lengan atas (sekitar 12-14 cm pada individu dewasa rata-rata
Panjang kantong balon harus sekitar 80% lingkar lengan atas (dengan panjang yang
mencukupi untuk melingkari lengan)
aneroid dikalibrasi secara berkala sebelum digunakan

Mempersiapkan Pengukuran Tekanan Darah :

-

Idealnya, meminta pasien untuk menghindari merokok atau minum minuman berkafein
selama 30 menit sebelum tekanan darah diukur dan untuk beristirahat selama
setidaknya 5 menit.
Pastikan ruang pemeriksaan tenang, nyaman dan hangat.
Pastikan lengan yang dipilih tidak tertutup pakaian. tidak boleh ada fistula arteriovenous
untuk dialisis, jaringan parut karena pemotongan arteri brakialis, atau tanda-tanda
lymphedema (terlihat setelah diseksi aksila atau terapi radiasi).
Palpasi arteri brakialis untuk memastikan denyut nadi masih aktif.
Posisikan lengan sehingga arteri brakialis berada pada lipatan antecubital, setinggi
jantung-kira-kira sejajar dengan interkostae 4 pada sambungannya dengan sternum.
Jika pasien duduk, istirahatkan lengan di atas meja sedikit di atas pinggang pasien; jika
berdiri, usahakan untuk menopang lengan pasien sejajar tinggi dada tengah.

Mengukur Tekanan Darah :

-

Tempatkan kantong balon di tengah arteri brakialis. Bagian tepi bawah manset harus
sekitar 2,5 cm di atas lipatan antecubital. Lingkarkan manset dengan tepat. Posisikan
lengan pasien sehingga sedikit fleksi di bagian siku.
Untuk menentukan seberapa tinggi menaikkan tekanan manset, pertama tentukan
tekanan sistolik dengan palpasi. Ketika Anda merasa arteri radial dengan jari satu
tangan, segera pompa manset sampai denyut nadi radialis menghilang. Baca nilai
tekanan ini pada manometer dan tambahkan 30 mmHg dari nilai yang didapatkan.
Gunakan penghitunag ini sebgai sasaran nilai untuk pemompaan selanjutnya sehingga
mencegah ketidak namanan karena tekanan tingguii maset yang tidak perlu. Hal ini juga
menghindari kesalahan tertentu yang disebabkan oleh kesenjangan auskultasi- suatu
interval diam antara tekanan sistolik dan tekanan diastolik.
Kempiskan segera manset dan tunggu 15 sampai 30 detik.

Sekarang tempat bagian bel stetoskop dengan hati-hati diatas arteri brakialis, pastikan
bahwa anda telah mengunci bagian ujung pengeluaran udara dengan memutar penuh
penutup udara. Karena suara yang didengar (bunyi Korotkoff) relatif berfrekuensi
rendah, terdengar lebih baik dengan bel stetoskop.
Kembangkan manset segera sekali lagi ke level hanya ditentukan, dan kemudian
kempiskan perlahan-lahan dengan laju penurunant sekitar 2 sampai 3 mmHg per detik.
Catatat tekanan ini jika anda mendengar suara setidaknya dua ketukan berturut-turut.
Tekanan ini merupakan tekanan sistolik
Terus menurunkan tekanan perlahan sampai suara menjadi teredam dan kemudian
menghilang. Untuk mengkonfirmasi hilangnya suara, dengarkan sampai tekanan turun
sekitar 10 sampai 20 mm Hg. Kemudian kempiskan manset secara cepat sampai ke nol.
Titikmenghilangnya suara detak jantung, biasanya hanya beberapa mmHg dibawah titik
munculnya suara, memungkinkan penentuan terbaik tekanan diastolik yang sebenarnya
pada individu dewasa

Baca level tekanan sistolik dan diastolik samapi yang terdekat dengan 2 mmHg. Tunggu
2 menit atau lebih dan ulangi. Rata-ratakan hasil pembacaan Anda. Jika dua bacaan
pertama memiliki perbedaan lebih dari 5 mm Hg, lakukan pembacaan tambahan.
Bila menggunakan sphygmomanometer merkuri, pastikan manometer vertical (Kecuali
jika Anda menggunakan model lantai miring) dan membuat semua garis bacaan di
tingkat mata dengan meniskus. Hindari inflasi lambat atau berulang pada manset,
karena dapat mengakibatkan kongesti vena yang menyebabkan pembacaan palsu.
Tekanan darah harus diambil pada kedua lengan setidaknya sekali. Biasanya, terdapat
perbedaan tekanan 5 mmHg dan kadang-kadang sampai 10 mm Hg.
Pada pasien yang memakai obat antihipertensi atau pasien dengan riwayat pingsan,
pusing postural, atau deplesi volume darah, ukur tekanan darah pada tiga posisiterlentang, duduk, dan berdiri (kecuali kontraindikasi). TUrunnya tekana sistolik 20
mmHg atau lebih, khususnya ketikadisertai gejala, menunjukka hipotensi ortotstatik
(postural).

Komplikasi/Kelainan Hati Akibat Diabetes Melitus

Sumber : Liver Disease and Diabetes Mellitus Gavin N. Levinthal, MD, and Anthony S. Tavill, MD,
FRCP, FACP (http://journal.diabetes.org/clinicaldiabetes/v17n21999/Pg73.htm)

1. Deposito glikogen
Sintesis glikogen di hati terganggu pada diabetes karena kegagalan aktivasi sintesis
glikogen. Pada pasien dengan diabetes kronis, terdapat akumulasi glikogen, yang menunjukkan
bahwa pasien lama kekurangan insulin. Mekanisme deposisi glikogen sitoplasma tidak pasti
tapi mungkin terkait dengan variasi yang besar dalam konsentrasi glukosa dan frekuensi dosis
insulin.
Mekanisme untuk deposisi glikogen nuklir juga tidak jelas, dengan glikogen yang
disimpan menyerupai glikogen otot lebih dari glycogen hati. Pasien dengan deposisi glikogen
dapat menunjukkan kelainan hepatomegali, kealinan enzim hati dan mungkin memiliki sakit
perut dan bahkan mual dan muntah dan jarang ascites. Semua kelainan ini dapat menurun
dengan memperbaiki control glukosa darah.
2. Fatty Liver, Steatohepatitis
akumulasi lemak hati merupakan komplikasi diabetes. Lemak disimpan dalam bentuk
trigliserida dan dapat merupakan manifestasi dari peningkatan transportasi lemak ke hati,
sintesis lemak hati meningkat, dan penurunan oksidasi atau penghilangan lemak dari hati.
Steatosis mungkin microvesicular atau macrovesicular dan dapat berkembang menjadi fibrosis
dan sirosis. Tingkat kontrol gula darah tidak berhubungan dengan ada atau tidaknya lemak.
klinis yang paling umum adalah hepatomegali, dan kebanyakan pasien memiliki atau hanya
transaminase sedikit tidak normal normal dan bilirubin normal.
Pola morfologi steatohepatitis diabetes menyerupai yang terlihat pada hepatitis alkoholik.
Namun, perubahan histopatologi pada diabetes cenderung periportal (terletak di zona I),
sedangkan pada hepatitis alkoholik didominasi pericentral (di zona III). Penurunan berat badan
secara bertahap dan kontrol kadar glukosa darah direkomendasikan untuk pasien dengan
steatohepatitis, penurunan berat badan> 10% terbukti mampu menormalkan kadar enzim hati.
3. Sirosis
Ada peningkatan insiden sirosis pada pasien diabetes. Diabetes meningkatkan risiko
steatohepatitis, yang dapat berkembang menjadi sirosis.
4. Komplikasi Terapi Diabetes

Terapi insulin dapat meningkatkan risiko patien tertular hepatitis virus karena paparan
jarum. Pengendalian infeksi yang baik secara signifikan mengurangi risiko ini.

Golongan biguanide yaitu metformin (Glucophage) tidak mengalami metabolisme

hepatik dan, seperti klorpropamid (Diabinese), tidak berubah setelah diekskresikan dalam urine.
Sebaliknya, glyburide sulfonylurea (Micronase, Glynase, Diabeta) diekskresikan dalam empedu
dan urin dalam 50 / 50 rasio. Sulfonylurea glipizide (Glucotrol, Glucotrol XL) dimetabolisme
terutama oleh hati, dan pada penyakit hati dapat mengakibatkan meningkatnya kadar obat
dalam darah.
Sulfonilurea dapat menyebabkan hepatitis kronis dengan perubahan necroinflammatory
dan perubahan granulomatosa. Klorpropamid merupakan yang paling hepatotoksik,
menyebabkan hepatitis kolestasis. Meskipun sangat jarang, acetohexamide dan glyburide
dapat menyebabkan nekrosis hepatoseluler akut. Biguanides, seperti metformin hidroklorida,
tidak dikaitkan dengan kerusakan hati.

Terapi DM pada Pasien dengan Gangguan Ginjal

Insulin
Insulin eksogen normal akan dimetabolisme di ginjal, sehingga pada gangguan fungsi
ginjal waktu paruh insulin akan memanjang karena turunnya kecepatan degradasi, oleh
karenanya pada pasien diabetes tipe 1 dengan gangguan fungsi ginjal episode hipoglikemia
meningkat 5 kali dibandingkan pasien dengan fungsi ginjal normal.
Belum ada rekomendasi jenis insulin yang harus dihindari atau dapat digunakan;
beberapa peneliti menyarankan agar menghindari penggunaan insulin dengan lama kerja
panjang, satu penelitian kecil membandingkan pasien diabetes dengan atau tanpa DKD
(Diabetic Kidney Disease) menunjukkan baik insulin regular dan insulin lispro mengalami
penurunan eliminasi, meskipun efektivitas insulin regular juga terganggu sehingga diperlukan
dosis yang lebih tinggi. Insulin lispro tidak menyebabkan perbedaan metabolisme glukosa pada
pasien dengan atau tanpa DKD, sehingga meskipun belum ada rekomendasi yang jelas, pasien
diabetes dengan penurunan fungsi ginjal yang mendapatkan insulin harus lebih diperhatikan
baik dalam penyusuaian dosis untuk mengkontrol glukosa darah maupun menghindari kejadian
hipoglikemia.
Terapi Oral Diabetes
Seperti halnya insulin, eliminasi beberapa obat juga menurun pada pasien dengan
gangguan fungsi ginjal yang juga akan memperpanjang paparan obat maupun metabolitnya
yang berpotensi meningkatkan efek samping. Eliminasi sulfonylurea dan metabolitnya sangat
dipengaruhi oleh fungsi ginjal, sehingga pada pasien PGK stadium 3-5 generasi pertama
sulfonylurea harus dihindari, tetapi generasi kedua yaitu glipizide dapat direkomendasikan oleh
karena metabolitnya tidak aktif dan risiko hipoglikemia jauh lebih rendah.
Meskipun mekanisme belum cukup jelas, obat diabetes alpha glukosidase inhibitor
dan metabolitnya dapat menyebabkan kerusakan akibat akumulasi dosis, sehingga tidak
diperbolehkan pada pasien dengan serum kreatinine > 2 mg/dL.
Metformin, tidak memperlihatkan efek samping hipoglikemia tetapi perhatian khusus
harus dilakukan pada pasien diabetes PGK karena risiko asidosis laktat, bahkan pada pasien
gangguan fungsi ginjal ringan, hal itu juga disebabkan akumulasi obat dan metabolitnya
sehingga kontraindikasi pada pria dengan klirens kreatinin > 1,5 mg/dL dan pada wanita dengan
klirens kreatinin > 1,4 mg/dL.
Thiazolidinediones (TZD) diduga memperlihatkan efek proteksi bahkan mencegah atau
memperlambat progresivitas DKD yang dipengaruhi oleh kontrol gula darah, beberapa
penelitian kecil memperlihatkan penurunan albuminuria pada pasien yang mendapatkan TZD,

obat ini di metabolisme di hati sehingga dapat diberikan bahkan pada pasien diabetes yang
menjalani dialisis tanpa perlu penyesuaian dosis.

Insulin

Bila dengan kombinasi 3 macam obat masih tidak mencapai target maka langkah
berikutnya adalah pengobatan insulin basal

Bila pasien datang dengan keadaan awal HbA1c 10,0% atau GDS 300 g/dl dengan
gejala metabolic, maka pengobatan langsung dengan :
a. Metformin + insulin basal insulin prandial
b. Metformin + insulin basal + GLP-1 RA

Indikasi terapi insulin

- HbA1c >9% dengan kondisi dekompensasi metabolic
- Penurunan berat badan yang cepat
- Hiperglikemia yang berat disertai dengan ketosis
- Krisis hiperglikemia
- Gagal dengan kombinasi OHO dosis optimal

Stress berat (infeksi sitemik, operasi besar, IMA, stroke)

Kehamilan dengan DM.DM gestastional yang tidak terkendali dengan perencanaan
makan
Gangguan fungsi ginjal atau hati yang berat
Kontraindikasi atau alergi terhadap OHO
Kondisi perioperatif sesuai dengan indikasi

Dasar Pemberian Terapi Insulin :

- Sasaran utama terapi hiperglikemia adalah mengendalikan gula darah puasa (basal).
Insulin yang dapat digunakan adalah insulin basal
- Penyesuaian dosis indulin basal untuk pasien rawat jalan dapat dilakukan dengan
menambah 2-4 unit setiap 3-4 hari bila sasaran belum tercapai
- Apabila sasaran glukosa darah basal telah terapai sedangkan HbA1c belum tercapai
maka dilakukan pengendalian glukoasa darah prandial. Insulin yang dipergunakan
adalah insulin kerja cepat yang disuntikkan 5-10 menit sebelum makan atau insulin kerja
pencek yang disuntikkan 30 menit sebelum makan

TREATMENT As in the non-CKD population, the treatment of nondialysis CKD and dialysis patients with diabetes
involves both nonpharmacologic and pharmacologic therapies [30].
The nonpharmacologic therapies include 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. (See "Initial management of blood glucose in adults with type 2 diabetes mellitus", section on
'Diabetes education'.)
Pharmacologic therapies include insulin and oral agents. Our approach varies depending upon whether patients are
on dialysis or not.
Nondialysis CKD patients For nondialysis CKD patients with type 2 diabetes, the choice of initial agent depends
upon glycemic goals (see 'Goals of therapy' above); the risk of medication-associated adverse events (hypoglycemia,
lactic acidosis); and patient preferences and convenience. Nondialysis CKD patients with type 2 diabetes 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 include short-acting sulfonylureas (eg,
glipizide) and repaglinide. 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. Glyburide and other long-acting sulfonylureas are generally not recommended in any
CKD patient with type 2 diabetes, because of the risk of hypoglycemia. Some clinicians recommend the use of the
meglitinide repaglinide (starting with a dose of 0.5 mg) for nondialysis CKD patients since these agents are not
renally cleared. (See "Initial management of blood glucose in adults with type 2 diabetes mellitus", section on 'Choice
of therapy' and "Sulfonylureas and meglitinides in the treatment of diabetes mellitus".)
Metformin, which is a preferred agent in patients without kidney disease, should not be used among CKD patients
with eGFR <30 mL/min/1.73 because of an increased risk of lactic acidosis [30]. However, we agree with the 2012
Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines that metformin may be used among patients with an
eGFR >45 mL/min/1.73 [18]. The use of metformin among patients with eGFR between 30 and 44 mL/min/1.73 is left
up to the discretion of the clinician, although the K/DOQI guidelines suggest that its use among individual patients be
reviewed. In general, we recommend leaving patients with this level of kidney function on metformin given the rarity of
complications and the clinical utility of metformin in maintaining glycemic control. Among all patients with GFR <60
mL/min/1.73 m2, metformin should be used with caution when the GFR is worsening at an unpredictable rate. (See
"Metformin in the treatment of adults with type 2 diabetes mellitus", section on 'Contraindications' and "Metformin in
the treatment of adults with type 2 diabetes mellitus", section on 'Lactic acidosis'.)
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.
(See "General principles of insulin therapy in diabetes mellitus" and "Insulin therapy in type 2 diabetes mellitus".)
Among patients who are treated with insulin, 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 (see "Carbohydrate and insulin metabolism in chronic kidney disease"). As a result, the
following dose recommendations have been made for insulin dosing in this setting [31-33]:

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
The initial dose of intermediate- or long-acting insulin in patients without CKD is approximately 10 units or 0.2 units/kg
(algorithm 1). Thus, in a patient with an eGFR between 10 and 50 mL/min, the initial dose would be approximately 7
units (75 percent of 10 units). The balance between altered insulin resistance and insulin clearance as renal
dysfunction progresses is difficult to predict in any individual patient, so insulin adjustment is often largely empiric.
Therefore, it is important that blood glucose levels be monitored closely and that individually appropriate dose
adjustments in insulin therapy be made.
Hemodialysis patients For most hemodialysis patients, we use insulin rather than oral agents. This is consistent
with the 2005 K/DOQI guidelines, which suggest that, among dialysis patients, newer insulin regimens and insulin
preparations should be used rather than oral agents for glycemic control [34]. This is due to the lack of adequate data
concerning the use of oral agents in dialysis patients and their inability to adequately excrete many such agents.
The principles of insulin therapy are the same for dialysis patients as for the general diabetic population. Several
different insulin regimens can be used to achieve glycemic control. Examples include twice-daily intermediate-acting
insulin, with regular insulin given before breakfast and before supper, or long-acting insulin, with two or three times
daily supplemental regular insulin, given two or three times per day before meals [35,36]. For hemodialysis patients,
the initial dose of insulin should be decreased by approximately 50 percent, as described above for nondialysis CKD
patients with GFR <10 mL/min. The dose should be titrated upward, as indicated by blood glucose monitoring. Most
patients will require more insulin than this initial dose. (See "General principles of insulin therapy in diabetes mellitus"
and "Insulin therapy in type 2 diabetes mellitus".)
A consensus approach does not exist to the choice of insulin in patients with diabetes and ESRD [32]. 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 [37]. Although repaglinide drug concentration
and elimination half-life are increased marginally in patients with reduced GFR, dose reductions are not necessary,
and this agent may be an appropriate therapy for patients with ESRD [38].
Peritoneal dialysis patients
Treatment regimens For patients who were already on an oral agent with good glycemic control prior to starting
dialysis, we typically continue the oral agent. For patients who develop diabetes after starting dialysis, we generally
treat first with an oral agent. However, over time, many peritoneal dialysis patients will require insulin.
As for nondialysis CKD patients, the preferred oral agent is glipizide. The dose for glipizide is 2.5 to 10 mg/day.
Repaglinide, which has minimal kidney clearance, is an alternative (starting with a dose of 0.5 mg/day). Metformin
should not be used among peritoneal dialysis patients, because of an increased risk of lactic acidosis [30].
Most peritoneal dialysis patients require insulin to maintain good glycemic control. Patients on continuous ambulatory
peritoneal dialysis (CAPD) or continuous cycler peritoneal dialysis (CCPD) who are being treated with insulin may be
treated with subcutaneous or intraperitoneal insulin. We prefer subcutaneous insulin. The principles underlying
subcutaneous insulin therapy are the same for nondialysis CKD patients as for the general diabetic population (see

"General principles of insulin therapy in diabetes mellitus" and "Insulin therapy in type 2 diabetes mellitus"). The initial
starting dose is similar to hemodialysis patients (decrease by approximately 50 percent), with upward titration based
upon blood glucose monitoring.
We, and most other nephrologists, do not use intraperitoneal insulin, since it often does not adequately control blood
sugars. Even among patients who achieve adequate glycemic control with intraperitoneal insulin alone, the required
insulin regimen is very complex since patients often alter CAPD schedules, as well as the timing of meals,
necessitating constant adjustment of the intraperitoneal insulin, which is burdensome for the patient.
Other disadvantages of intraperitoneal insulin include the risk of bacterial contamination of dialysate during injection
of insulin into the bags [39]; the requirement for a higher total insulin dose due to losses into spent dialysate and to
binding to the plastics in bags and tubing [40-43]; and an associated risk of peritoneal fibroblastic proliferation [44]
and, perhaps, of hepatic subcapsular steatosis [40]. Another potential concern is that the absorption of insulin may
significantly vary among patients or may decline over time in a single individual due to acquired abnormalities in the
peritoneal membrane [45]. One study of seven patients suggested that the latter is not a common problem, as there
was no difference in insulin absorption after 30 months of CAPD [46].
There are no long-term studies evaluating use of intraperitoneal insulin. A meta-analysis of three trials demonstrated
better glycemic control, as assessed by HbA1c, with intraperitoneal compared with subcutaneous insulin in CAPD
patients, but the insulin dose was more than double with intraperitoneal use [47]. Patients treated with intraperitoneal
insulin had lower high-density lipoprotein (HDL) cholesterol levels and higher triglyceride levels compared with those
treated with subcutaneous [47].
Abnormal or variations in peritoneal kinetics The above recommendations regarding the treatment of peritoneal
dialysis patients assume that peritoneal transfer kinetics are relatively normal. Diabetic patients on CAPD who have
uncontrolled hyperglycemia should undergo a peritoneal equilibration test. (See "Peritoneal equilibration test".)
High transporters, who can have enormous glucose loads from rapid peritoneal glucose absorption (figure 1), will
usually benefit from transfer to nocturnal automated peritoneal dialysis [40,48]. In addition to raising the blood
glucose, the rapid glucose absorption lowers the osmotic gradient between dialysate and blood, resulting in reduced
ultrafiltration, diminished urea removal, and fluid retention. A vicious cycle is then created, with generalized edema
requiring frequent use of 2.5 and 4.25 percent dextrose dialysis solutions, leading to further hyperglycemia.
Carbohydrate-sparing dialytic regimens Adjusting the peritoneal dialysis solution may improve glycemic control in
some patients. Glucose polymers were introduced to replace glucose-containing solutions by offering the possible
advantages of decreased absorption of solute and increased ultrafiltration for a longer period of time. The use of a
glucose polymer as an osmotic agent is particularly appealing as a substitute for glucose solutions, particularly in
patients with diabetes [49].
Carbohydrate-sparing dialytic regimens include:
Icodextrin, in which carbohydrate absorption is equivalent to a 2.5 percent dextrose bag, but is associated with
ultrafiltration of a 4.25 dextrose bag [50]
Amino acid dialysate solutions, which are available in countries outside the United States
This topic is reviewed in detail elsewhere. (See "Peritoneal dialysis solutions".)
ORAL AGENTS 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 [31,32,51]. (See "Initial

management of blood glucose in adults with type 2 diabetes mellitus", section on 'Initial pharmacologic therapy' and
"Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'Treatment options'.)
Sulfonylureas Glipizide is the sulfonylurea of choice in patients with CKD. The dose for glipizide is 2.5 to 10
mg/day. (See "Sulfonylureas and meglitinides in the treatment of diabetes mellitus".)
The administration of sulfonylureas in ESRD requires careful attention to dosing and routes of elimination
[32,33,52,53]. The sulfonylureas are strongly protein bound, particularly to albumin [52]. Thus, elevated plasma drug
levels cannot be efficiently reversed by hemodialysis. Furthermore, displacement of these drugs from albumin by beta
blockers, salicylates, and warfarin can lead to hypoglycemia due to increased plasma concentration of the
physiologically important free drug. Older sulfonylureas (acetohexamide, chlorpropamide, tolazamide, and
tolbutamide) have been largely replaced by newer agents such as glyburide, glipizide, and glimepiride.
The basic principles of sulfonylurea metabolism can be summarized as follows:
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 [32].
Glipizide and tolbutamide are metabolized by the liver and primarily excreted in the urine as inactive metabolites.
However, each has one metabolite that may have weak hypoglycemic activity.
Meglitinides Meglitinides, such as repaglinide or nateglinide, are sulfonylurea-like agents that stimulate insulin
secretion [32]. (See "Sulfonylureas and meglitinides in the treatment of diabetes mellitus".)
Repaglinide is principally metabolized by the liver, with less than 10 percent renally excreted [32]. Hypoglycemia may
be more common among patients with advanced CKD when starting therapy with repaglinide than among subjects
with normal or less impaired kidney function, and maintenance doses tended to be lower in these patients in one
study [38]. Initiation of treatment should be with 0.5 mg daily; close, careful monitoring of blood glucose levels is
essential as the dose is titrated.
Nateglinide is hepatically metabolized, with renal excretion of active metabolites. With decreased kidney function, the
accumulation of active metabolites and hypoglycemia has occurred [54,55]. This drug must therefore be used
cautiously in this setting, if at all.
Dipeptidyl peptidase 4 (DPP-4) inhibitors Although some DPP-4 inhibitors have been studied in patients with
kidney dysfunction, the data are limited, and, therefore, we suggest not using DPP-4 inhibitors among such patients.
However, limited data suggest that these agents are effective and relatively safe in CKD and ESRD patients [56,57].
Dose adjustments are needed for some agents in this class.
DPP-4 is an enzyme expressed on the surface of most cell types that deactivates the incretin hormones glucagon-like
peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). DPP-4 inhibitors cause a glucosedependent increase in insulin release. The use of DPP-4 inhibitors in patients without ESRD is discussed elsewhere.
(See "Dipeptidyl peptidase 4 (DPP-4) inhibitors for the treatment of type 2 diabetes mellitus", section on
'Candidates'.)
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 [58]. Sitagliptin is largely excreted in the urine, with 70 to 80 percent of
an oral dose appearing unchanged in the urine [59]. If sitagliptin is used among ESRD patients, a dose reduction to
25 mg daily (usual dose 100 mg daily) is recommended. Although sitagliptin is partially cleared by hemodialysis, it
may be given without regard to the timing of dialysis [60]. Information on the use of sitagliptin in ESRD patients is

limited [61], but it appears to have equal efficacy to glipizide [56,57]. 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 [62]. Saxagliptin was reported to be well tolerated in a single small study [63]. Vildagliptin also appears
to be effective in this population in limited study [64].
Thiazolidinediones Given the risk of edema formation and heart failure, as well as possible increased mortality with
rosiglitazone, thiazolidinediones should be avoided in patients with advanced CKD, especially if they have preexisting heart failure.
Thiazolidinediones enhance tissue sensitivity to insulin and suppress hepatic glucose production via binding to
peroxisome proliferator-activated receptor (PPAR) gamma [65]. (See "Thiazolidinediones in the treatment of diabetes
mellitus".)
Hemodialysis does not affect the pharmacokinetics of these drugs.
Rosiglitazone, which is infrequently used and has US Food and Drug Administration (FDA) restrictions independent of
kidney function, and pioglitazone are highly protein bound, primarily to albumin, and almost completely metabolized
by the liver [32]. In an observational study, the use of rosiglitazone was also associated with increased all-cause and
cardiovascular mortality in hemodialysis patients [66]. Rosiglitazone has inactive metabolites, and <1 percent of the
original compound is excreted in the urine; pioglitazone is associated with three active metabolites. With both agents,
the accumulation of the parent drug or the major metabolites does not occur in the setting of CKD.
These agents are associated with heart failure and the formation of edema, which may be more frequent in patients
also receiving insulin [32]. The mechanism of edema formation with these agents appears to be related to stimulation
of PPAR gamma-mediated sodium reabsorption by renal epithelial sodium channels in the distal tubule [67].
Thiazolidinedione-associated edema may not pose a problem for oliguric or anuric dialysis patients. Although
unproven clinically, amiloride, spironolactone, or similar agents may therefore be effective for managing this fluid
retention.
Alpha-glucosidase inhibitors Alpha-glucosidase inhibitors, such as acarbose or miglitol, are not recommended in
patients with renal dysfunction [32].
These agents slow carbohydrate absorption from the gastrointestinal tract and reduce postprandial blood sugar
peaks. (See "Alpha-glucosidase inhibitors and lipase inhibitors for treatment of diabetes mellitus".)
With acarbose, increased levels of the parent drug and metabolites are observed with CKD, although an increased
risk of hypoglycemia has not been documented. Miglitol is absorbed to a greater extent than acarbose and is largely
renally excreted, with increased accumulation in patients with decreased kidney function.
Metformin Biguanides, such as 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 [32]. (See "Metformin in the treatment of adults with type 2 diabetes
mellitus".)
Sodium-glucose cotransporter-2 (SGLT-2) inhibitors These agents, several of which have been approved for use
alone or in combination with others agents in the US, including dapagliflozin, canagliflozin, and empagliflozin, inhibit
glucose absorption in the proximal tubule, causing glucosuria, weight loss, and improved glycemic control. Use of
these medications is not recommended with an estimated glomerular filtration rate (eGFR) <45 to 60 mL/min/1.73
m2, and they are contraindicated with eGFR <30 mL/min/1.73 m2, including patients with ESRD who are on dialysis
[68-70]. These drugs have also been implicated in causing diabetic ketoacidosis in individuals with type 1 and type 2

diabetes [71]. (See "Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'SGLT2
inhibitors'.)
APPROACH TO PROBLEM PATIENTS Some diabetic patients have persistent hyperglycemia, severe
hyperglycemia, diabetic ketoacidosis, frequent hypoglycemia, or alternating episodes of hyperglycemia and
hypoglycemia.
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) [72].
An additional problem is that microvascular disease can cause erratic absorption of insulin from the subcutaneous
tissue, particularly if the patient does not rotate injection sites [41]. (See "General principles of insulin therapy in
diabetes mellitus", section on 'Site of injection'.) The approach to these issues is the same for CKD patients as for
non-CKD patients and is discussed elsewhere. (See "General principles of insulin therapy in diabetes mellitus",
section on 'Determinants of insulin efficacy' and "Management of persistent hyperglycemia in type 2 diabetes
mellitus", section on 'Indications for a second agent'.)
Severe hyperglycemia and ketoacidosis Severe hyperglycemia, with serum glucose concentrations occasionally
>1000 mg/dL (55 mmol/L), may be observed among dialysis patients with diabetes. Unlike those without 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 [73].
However, these patients may have marked hyperkalemia due to potassium efflux from cells in response to
extracellular fluid hypertonicity, as well as hyponatremia and acute intravascular volume expansion [74]. Patients with
type 1 diabetes may also develop diabetic ketoacidosis.
Instead of fluid replacement, management is principally dependent upon the administration of low doses of
intravenous insulin (commonly beginning at a dose of 2 units/hour) [73]. As with nondialysis patients with severe
hyperglycemia and diabetic ketoacidosis, serum glucose and potassium concentrations must be closely monitored.
(See "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Treatment", section on 'Monitoring'.)
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 (see "Prescribing and assessing adequate hemodialysis" and "Prescribing and assessing adequate
peritoneal dialysis" and "Protein intake in maintenance hemodialysis patients" and "Assessment of nutritional status
in end-stage renal disease"). 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 [41], which
complicates the timing of insulin injections. Gastric-emptying studies will confirm the diagnosis, which can often be
effectively treated with metoclopramide or bethanechol (urecholine) [41]. Improvement in glycemic control may also
improve gastric motility. (See "Diabetic autonomic neuropathy of the gastrointestinal tract", section on
'Gastroparesis'.)
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, and 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. (See "The adult patient with brittle
diabetes mellitus".)