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Therapy to Slow Diabetic Nephropathy

Progression
Kunci

perawatan medis untuk pasien diabetic nephropathy meliputi:


Glycemic control
Management of hypertension
Management of albuminuria
Dietary changes

GLYCEMIC CONTROL

Hyperglicemia merupakan major determinant untuk progresi dari diabetic nephropathy


terutama pada pasien DMT1. Terapi intensif terhadap hiperglikemi mampu: partially reverse
glomerular hypertrophy and hyperfiltration, delay development of microalbuminuria, and
stabilize or even stabilize microalbuminuria. Bahkan pada Diabetes Control and Complications
Trial (DCCT), menunjukkan bahwa efek paling kecil pengendalian kadar gula dalam darah
adalah berupa reduction in microvascular complication.
British and US recommendations are to establish and maintain tight blood glucose control in
<7% HbA1c.
Newer agents in diabetic patients with kidney disease
oDipeptidyl peptidase inhibitors: DPP4 inhibitor (ie, gliptins) are new class of antidiabetic
agents that can be used in DMT2. Cara kerjanya adalah dengan menghambat
breakdown dari incretin hormones seperti glucagonlike-peptide 1 (GLP-1) yang
disekresikan oleh GI tract sebagai respon terhadap food intake and leads to insulin
secretion in glucose dependent manner- while also decreasing glucagon release.
Contoh agents: sitagliptin, saxagliptin, linagliptin, dan alogliptin.
oAlpha-glucosidase inhibitors: bekerja dengan menurunkan pemecahan oligosakarida
dan disakarida pada small intestine sehingga memperlambat penyerapan glukosa
setelah makan.
Contoh agents: acarbose dan miglitol.
oSodium-glucose cotransporter 2 (SGLT2) inhibitors: menghambat renal glucose
absorption in proximal tubule yang merupakan tempat terjadinya 90% reabsorpsi
glukosa di ginjal sehingga meningkatkan ekskresi glukosa di urin sekaligus juga
meningkatkan ekskresi sodium which in turn may help with further blood pressure
lowering.
Contoh agents: canagliflozin (invokana)
oGlucagonlike peptide-1 (GLP-1) receptor agonistsor incretin mimetics: bekerja dengan
meng-enhace central satiety and reduce appetite, thus helping weight loss. These
drugs promote insulin release, delay glucagon release, and slow gastric emptying and
are less likely to cause hypoglycemia.
Contoh agents: exenatide (Byetta) dan liraglutide (Victoza)
oAmylin analogs: Kerjanya adalah sebagai complementary to insulin in regulating
plasma glucose concentration. Ia juga turut melambatkan pengosongan lambung,
reduce postprandial glucagon, and can suppress appetite.
Contoh agents: pramlintide (symlin)

MANAGEMENT OF HYPERTENSION

Secara umum, terapi hipertensi memperlambat perkembangan diabetic glomerulopathy. Hasil


penelitian UKPDS menunjukkan 12% risk reduction in diabetic complications was found with
each 10mmHg drop in systolic blood pressure, the lowest risk being associated with systolic
pressure <120mmHg.
ACE inhibitors
Long-term treatment with ACE inhibitors, usually combined with diuretics, reduces BP and
albuminuria and protects kidney function, by delaying diabetic nephropathy development
and also associated with normal GFR preservation, in patients with hypertension, DMT1,
and nephropathy.

Terapi dengan ACE-inhibitor selama 12 bulan pada pasien DMT2 dengan mikroalbuminuria
menunjukkan adanya penurunan mean arterial blood pressure and urinary albumin
excretion.
Angiotensin receptor blockers (ARBs) for RAS inhibiton
RAS inhibiton is effective in treating type 1 and type 2 diabetic nephropathy. ARBs is
superior to conventional therapy and amlodipine in slowing the progression overt
nephropathy.
Direct renin inhibitors
Contoh agennya adalah aliskiren dan penggunaannya sudah tidak lagi direkomendasikan
oleh FDA sejak April 2012 karena isu serious side effects. Namun penelitian menunjukkan
bahwa vitamin D may have a role in renin inhibition sehingga suplementasi vitamin D may
be useful in reducing proteinuria in patients with diabetic nephropathy.
Endothelin antagonist therapy
Endothelin antagonist menunjukkan efek antifibrotik, anti-inflammatory, dan antiproteinuric
pada experimental studies. Penggunaannya biasa ditambahkan pada terapi dengan ACE
inhibitor atau ARB untuk bisa menurunkan mean relative urinary albumin excretion rate.

MANAGEMENT OF ALBUMINURIA

KDOQI (Kidney Disease Outcomes Quality Initiative) Clinical Practice Guidelines and Clinical
Practice Recommendations for Diabetes and Chronic Kidney Disease menggaris bawahi
management albuminuria. Data sebelumnya menunjukkan bahwa captopril could reverse
proteinuria in patients with diabetes-related nephropathy. Captopril therapy led to remission
of nephrotic proteinuria (>3.5g/d) in 16.5% pasien, compared with 1.5% of those with placebo
(P=0.005). Remission of proteinuria was associated with achieving a lower systolic BP.

DIETARY CHANGES

Perubahan diet meliputi: protein restriction 0.5-0.85 g/kg BW/day suggested a beneficial effect
on GFR, creatinine clearance, and albuminuria; phosphorus and potassium restriction with the
use of phosphate binders in advanced cases; and dietary salt reduction <5-6g/d.

Renal Replacement Therapy Option in ESRD


caused by Diabetic Nephropathy
As for any other patient with ESRD, diabetic patients with ESRD can be offered renal
replacement therapy. In patients with diabetic nephropathy, starting at a creatinine clearance
or estimated GFR (eGFR) of 10-15mL/min is wise. In diabetic patients, starting earlier is useful
when hypervolemia renders BP uncontrollable, when the patient experiences anorexia and
cachexia or other uremic symptoms, and when severe vomiting is combined result of
uremia and gastroparesis.
Pada prinsipnya, pasien diabetes yang memerlukan RRT memiliki 4 opsi:
Refusal of further treatment for uremia, leading to a progressive decline in general
health and ultimately leading to death
Peritoneal dialysis (eg, machine-assisted intermittent peritoneal dialysis, continuous
ambulatory peritoneal dialysis, continuous cyclic peritoneal dialysis)
Hemodialysis (eg, facility hemodialysis, home hemodialysis)
Renal transplantation (eg, cadaver donor kidney, living related-donor kidney, living
unrelated-donor kidney [emotionally related donor], living unrelated-donor kidney
[unrelated by family or emotonally; this so-calles altruistic donor], pancreas plus kidney
transplantation)