COMPARISONBETWEENGLYCOGENLEVELOFKIDNEYTUBULAR

CELLS INDIABETICKIDNEYSTONEPATIENTS ANDNONDIABETIC

KIDNEYSTONEPATIENTS
1 1 1 1 1 1
Ken Ramadhan, Suwandi Sugandi, Bambang S. Noegroho, Tjahjodjati, Ferry Safriadi, Safendra
1 1 1 2
Siregar, Ricky Adriansjah, Kuncoro Adi, Aaron TigorSihombing, Makmuri Yusuf.
1
Department oI Urology, Faculty oI Medicine/Padjadjaran University, Hasan Sadikin Hospital, Bandung.
2
Department oI Pathology, Faculty oI Medicine/Padjadjaran University, Hasan Sadikin Hospital, Bandung.
ABS1RAC1
Objective: To compare glycogen level of kidney tubular cells in diabetic kidney stone patients with nondiabetic kidney
stone patients. Material & method: We reviewed kidney stone patients who underwent nephrectomy in Hasan Sadikin
Hospital from February 2008 to January 2009. Age, gender, type of diabetes mellitus, and urine pH were recorded.
Glycogen level of kidney tubular cells were evaluated histochemically using HE, PAS, and PAS diastase. The results
were categori:ed into 3 grades, based on the staining appearance compared to liver cells as controls. The results of
diabetic group were compared to non diabetic patients. Results: There were 30 patients eligible for this study, 15 in
diabetic group and 15 non diabetic patients. In the diabetic group, there were 10 patients with urine pH 6 and 5
patients with a pHof 6,5. In the non diabetic group all urine pHwere ~6,5. Examination revealed that glycogen level of
kidney tubular cells in diabetic group was higher than in non diabetic group. Conclusion. Glycogen level of kidney
tubular cells in diabetic kidney stone patients was higher than in non diabetic kidney stone patients.
Keywords: Tubular cell, kidney stone, diabetes mellitus.
Correspondence: Ken Ramadhan, c/o: Department oI Urology, Faculty oI Medicine/Padjadjaran University, Hasan Sadikin
Hospital. Jl. Pasteur No. 38, Bandung 40161. Phone: 022-2039141. Email: kenramadhanyahoo.com.
INTRODUCTION
Prevalence oI diabetes mellitus (DM) is
increasing in Indonesia. Multiple organ complications
can involve the kidney, termed diabetic nephropathy
1
caused by diabetes mellitus. Some studies show an
increasing incidence oI stone Iormation in diabetic
nephropaty. An observational study by Curhan et al
shows that stone Iormation is related to systemic
disease such as diabetes mellitus in a multiIactorial
2,3
process.
Insulin resistance plays an important role in non
insulin dependent diabetes and is associated with
2
Iormation oI uric acid stones. Pak and colleagues
noted a higher prevalence oI uric acid stones and a low
urinary pH in patients with non insulin dependent
diabetes (34) than among non diabetic stone
2,3
Iormers. Impaired ammonium production or
secretion as a result oI insulin resistance could leave
hydrogen ions unbuIIered in the urine, which leads to
reduction oI urine pH. Insulin resistance also inhibits
gluconeogenesis, which might be associated with a
4
low urine pH that will lead to stone Iormation. The
purpose oI this study is to compare the glycogen level
oI kidney tubular cells in stone patients with and
without diabetes mellitus innondiabetic kidney.
OB1ECTIVE
To compare glycogen level oI kidney tubular cells
in diabetic kidney stone patients with in non diabetic
kidney stone patients.
MATERIAL& METHOD
This study is a cohort retrospective study to
review glycogen level oI kidney tubular cells in
diabetic kidney stone patients compared to non
diabetic kidney stone patients.
We reviewed kidney stone patients who under-
went nephrectomy in Hasan Sadikin Hospital Irom
27
February 2008 to January 2009. Age, gender, type oI
DM, and urine pH oI the participants were notiIied.
Glycogen level oI kidney tubular cells were evaluated
histochemically using HE, PAS, and PAS diastase. The
results were categorized into 3 grades, based on
staining intensity using liver cells as controls. The
results oI diabetic group were compared with non
diabetic group. Statistical signiIicance was evaluated
with the student t-test.
RESULTS
From February 2008 until January 2009 at Hasan
Sadikin Hospital, 30 patients underwent nephrectomy,
15 patients with, and 15 without diabetes. In the
diabetic group, 10 patients had urine pH 6 and 5
patients had urine pH oI 6,5. In non diabetic group all
urine pHwere ~ 6,5.
Histochemical examination showed that glycogen
level oI kidney tubular cells in diabetic group was
higher than in non diabetic group in all samples.
Twelve samples in non diabetic group had lower
glycogen levels while 3 samples were higher. Analysis
using t-test showed higher glycogen level in diabetic
group compared to non diabetic group.
DISCUSSION
Several Iactors contribute to the Iormation oI
urinary lithiasis. Low urinary pH is one oI the most
4
important Iactor. The mechanism by which insulin
resistance leads to low urine pH is not know. Insulin
resistance itselI plays an important role in non insulin
dependent diabetes and is associated with uric acid
2,5,6
stone Iormation. Pak and colleagues noted higher
prevalence oI uric acid stones and low urinary pH
among patients with non insulin dependent diabetes
2
(34) than among non diabetic stone Iormers.
Sakhaee and colleagues Iirst observed that
normouricosuric individuals with pure uric acid
stones were more likely to have diabetes mellitus or to
demonstrate glucose intolerance than normal
individuals or those with mixed uric acid/calcium
oxalate or pure calcium oxalate stones. Furthermore,
when a group oI normouricosuric uric acid stone
Iormers were placed on a controlled metabolic diet,
their urinary pH was lower than that oI either normal
volunteers or other stone Iormers (mixed uric
acid/calcium oxalate or calcium oxalate). Further
investigation revealed that uric acid stone Iormers
excreted less acid into the urine as ammonium and
proportionately more titratable acid and less citrate in
order to maintain normal overall acid-base balance.
This apparent impairment in ammonium excretion in
uric acid stone Iormers has been putatively linked to
2-4
aninsulinresistant state.
Abate and colleagues (2004) perIormed
hyperinsulinemic euglycemic clamps to measure
insulin sensitivity in a diverse group oI non stone
Iorming and a group oI uric acid stone Iormers. They
Diabetic mellitus group
Non diabetic mellitus group
28
Control (hepar)
JURI, Vol. 18. No. 1. January 2011: 27-30
Iound that among normal subjects, low urinary pH
corellated with lowrates oI glucose disposal. Uric acid
stone Iormers displayed the most severe levels oI
insulin resistance. This association oI insulin
resistance and low urinary pH was Iurther
corroborated by the Iinding oI a strong inverse
association oI body weight (known to be associated
with peripheral insulin resistance) and urinary pH,
even aIter adjusting Ior urinary sulIate (a marker oI
2
animal protein intake) (MaalouI et al, 2004b).
Insulin resistance can cause impaired ammonium
production or excretion in kidney tubular cells which
leading to reduction in urine pH. Alternatively,
increased amounts oI Iree Iatty acids and inhibited
gluconeogenesis in insulin resistance can also cause
7-9
reduction in urinary pH (Iigure 1). Study in USA
noted there was increase in Iree Iatty acid level in
kidney tubular cells in rats aIter consumption higher
Iat diet. Increased in Iree Iatty acid is associated with
10
lowurinary pH. Glycogen level in cells is increase iI
there is inhibition in gluconeogenesis, but we have not
know yet in kidney tubular cells. II mechanism in
Iigure 1 really happen, glycogen level in kidney
Urine
+ nsulin stimulation
Plasma
Glutamine
GIutaminase
Glutamate
GIutamate
dehydrogenase
Gluconeogenesis
Citric acid cycle
ATP
(n) Fatty acid
(n-2) Fatty acid
Acetyl-CoA
+
NH
4
NH
3
NHE3
+
H
+
H
+
Na
+
Na
+
NH
3
-Ketoglutarate
NHE3
+
NH
4
+
NH
4
+
+
Figure 1. Insulin eIIect in ammonium production and secretion in kidney tubular cells
29
tubular cells can increase in insulin resistance like
diabetes mellitus patients.
This study showed glycogen levels in kidney
tubular cells were higher in diabetic group. This
condition is associated with lower urinary pH in
diabetic group. These results shows insulin resistance
plays a role in kidney stone Iormation in patients with
diabetes. This supports a relationship between low
urinary pH with insulin resistance which may explain
mechanism oI kidney stone Iormation in diabetic
patients. The result oI this study can be applied as a
guide to prevent stone Iormation in diabetes mellitus.
Because oI persistently lowurine pH, alkalinization oI
the urine in diabetic patients is important. With
alkalinization oI the urine, we can maintain the balance
oI urine pH. In addition, early control oI blood glucose
level in diabetic patients to prevent insulin resistance is
also important.
CONCLUSION
This study concluded that glycogen level oI
kidney tubular cells in diabetic kidney stone patients
were higher than innondiabetic kidney stone patients.
Ramadhan: C omparison between glycogen level oI kidney tubular cells
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