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Jonny
ABSTRACT
Disclaimer: The views expressed in this article is individual and not an official position of the
institution or any other parties.
Diabetes Mellitus (DM) is currently developing epidemically around the world due to
[1]
lifestyle changes . According to WHO (World Health Organization), the number of DM
patients increased from 108 million in 1980 to 422 million in 2014, and is expected to be 642
million by 2040.[2,3] Diabetic Nephropathy is one of the major complications affecting about
one-third of DM patients of either type one or two3 characterized by progressive renal mass
expansion due to accumulation of extracellular matrix (ECM) in the form of collagen IV,
laminin, fibronectin, proteoglycans, etc.{4,5] The concept of Diabetic Nephropathy is now
transformed into Diabetic Kidney Disease (DKD). The concept of Diabetic Nephropathy
emphasizes a clear definition and identification of kidney disease, while the concept of
Diabetic Kidney Disease emphasizes the complexity and heterogeneity of kidney disorders in
DM patients.[6]
The parameters used to assess Diabetic Kidney Disease are proteinuria, which
consists of macroalbuminuria and microalbuminuria.[7] Microalbuminuria showed an increase
in urine albumin excretion as much as 30-299 mg/g creatinine. While macroalbuminuria is
when it is excreted more than 300 mg/g creatinine. A more accurate examination for
assessing proteinuria today is with UACR (Urinary Albumine Creatinine Ratio).[8]
One of the alternative therapies for reducing proteinuria in Diabetic Kidney Disease is
by using Lumbrokinase, which includes Traditional Chinese Medicine. Lumbrokinase is an
extract from one type of a worm in class Lumbricus rubellus that contains bioactive
proteolytic enzymes. Studies show that Lumbrokinase has anti-inflammatory, antioxidant,
fibrinolytic, antimicrobial, and anticancer effects.[9-13] Lumbrokinase is a proteolytic enzyme
that acts as a plasminogen activator and serine protease-specific fibrin. The mechanism of
action is similar to tissue activator plasminogen (t-PA) which has thrombolytic activity when
there is fibrin. Lumbrokinase also divides fibrinogen and fibrin.[14]
Patients are given Lumbrokinase (Tromboles®) 250mg with a dose of 3x2 capsules
daily for 12 weeks. Before Lumbrokinase was given, laboratory parameters such as
proteinuria (UACR), serum fibrinogen level, serum urea, and serum creatinine were
examined. The estimated glomerular filtration rate was calculated based on the serum
creatinine level with the modified diet renal disease (MDRD) equation. Laboratory
parameters are checked again every 4 weeks (monthly) consecutively for 12 weeks.
Results
After Lumbrokinase was given for 12 weeks, results obtained are shown in table 1.
While the other parameters did not appear to differ significantly between before and
after Lumbrokinase administration, although the mean urea serum, creatinine, and eLFG
level is decreasing.
Discussion
Besides two function mentioned above, Lumbrokinase is also known has function as
anti-ischemic. Animal experimental test indicate that this anti-ischemic is due to anti-platelet
activity because it increases cAMP and calcium release from calcium stores in cells;
antithrombotic activity due to resistance to intercellular adhesion molecule-1 expression
(ICAM-1); and anti-apoptotic effect due to the activation of janus kinase-1/signal transducers
and activators of transcription-1 (JAK1/STAT1).[25] Jin et al study on 51 patients with
cerebral infarction given Lumbrokinase 3x400mg for 28 days showed the lengthening of
kaolin partial thromplastin time (KPTT), increased t-PA, decreased D-dimer level, and
decreased fibrinogen level.[26]
In our study, there was a decrease in fibrinogen serum level although not statistically
significant. This is consistent with Fei et al study on 20 patients with nephrotic syndrome that
showed administration of Lumbrokinase 230mg with dose 3x2 capsules for 4 weeks
significantly decreased fibrinogen serum level (p <0,001).[16] Similarly in Chung et al study,
study on 50 patients with cerebral infarction after 3 weeks of attack showed that 3x2 capsules
Lumbrokinase for 4 weeks decreased fibrinogen serum level significantly (p <0,001).[29]
Fibrinogen serum level also decreased significantly (p <0,001) in Shu and Minghua study on
31 patients with Retinal Vein Obstruction (RVO) with Lumbrokinase dose 3x460mg for 3
months.[30] Xin et al’s study on 20 patients with unstable angina showed fibrinogen serum
level decreased with Lumbrokinase dose 3x2 capsules for 10-14 days.[31]
Fibrinogen serum level in our study also appeared to decrease after administration of
Lumbrokinase 230mg with dose 3x2 capsules for 12 weeks, but not significantly. The
seemingly “neutral” effect on fibrinogen level seen in this study might be confounded by
several factors and can disrupt the results. Previous studies have shown that the fibrinogen
synthesis is influenced by several conditions such as high protein intake, long smokers,
progesterone effects during luteal phase in women.[32] Limitations in this study are small
samples and do not measure the fibrin/fibrinogen degradation products (FDPs) which can
assess more definite fibrinogenolytic activity.
Reduction of MMP2 and MMP9 can suppress ECM degradation and accelerate the
progression of diabetic nephropathy. Lumbrokinase can up-regulate MMP2 and MMP9
thereby reducing type 4 collagen deposition that will reduce proteinuria and suppress the
progressivity of diabetic nephropathy.[15] Fei et al study showed a significant decrease in
proteinuria (p <0,01) after Lumbrokinase administration.[16] Reduced proteinuria was also
observed in Hu Hai and Jia Ru study after administration of Lumbrokinase orally for 20 days,
although the reduction was not significant (p > 0,05).[17] In our study, there was no
statistically significant decrease of proteinuria (p = 0,075) which marked by decreased
UACR. The UACR level was seen to decrease from 813,33mg/g to 447,17 mg/g after 12
weeks Lumbrokinase administration (Table 1).
Conclusion
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