Additionally, vital progress has been attained within the
pathologic process of uric acid and calcium stones that check with the
connection between them ,and thus affected the event of treatment of this sort
of stones (9). Many studies
had documented the role of hyperuricosuria within the development of the
monosodium urate which would lead to calcium stones (10).
Because of the continual increase in number within the prevalence
of diabetes patients (11), and their square measure several studies
reported that diabetic patients eject through urinating additional uric acid ,
especially in patients with a history of renal stones; few studies investigated
the variations of urine composition between diabetic and non-diabetic patients
in non-stone-forming people;in our study,we are going to concentrate on urine
composition of diabetic patients in non-stone formers.
Our original hypotheses was that there are no mean variations
of uric acid excretion with relation to diabetic and non-diabetic patients in
24-hour urine composition, but in the event our results did not support this
view.
MATERIALS
AND METHODS
A (sample of
420 patients)were registered during this retrospective study which was created
in our Prince Hussein Bin Abdullah the Urology center of the Royal Medical
Services. These patients were seen and examined within the urology clinics
between (June of 2015 and August of 2018). The ages of those participants were
ranging between (21 and 66 years); our analysis assistant divided these
patients into two groups: two main groups:
group-1 which comprised 210 type II diabetics patients, and group-2
which comprised 210 not diabetics patients who were diagnosed to have illness
free by the medical history, normal fasting vs. postrandial glucose levels and
HBA1C when available in the medical records of those patients.
This study has enclosed and
separated the patients who have (inclusion criteria): type Π diabetes > 1
year duration , diabetics with retinopathy or neuropathy, benign prostatic
hypertrophy or prostate carcinoma, urinary tract infections or tumors, renal
pathologies apart from stones like (tumors, cysts, pelvic ureteric obstruction
and congenital abnormalities), urine bladder pathologies like (tumors,
infections either acute or chronic and interstitial cystitis), testicular
pathologies like (varicocele, hydrocele and tumors), normal kidney functions
tests, normal coagulopathy profile and hypermetabolic syndrome risk factors
(HTN, Hyperlipidemia and obesity); taking into consideration that the exclusion
criteria were: Whereas the exclusion criteria were: ages less than twenty-one
years, diabetics with nephropathy, patients with chronic diarrhea, liver
disease, hyperparathyroidism patients, pregnancy, stone formers, patients with a
history of recent hematuria, urine bladder stone patients, patients on
dialysis, patients with neurogenic bladder and patients with a history of gouty
diathesis.
The data of 24- hours collected urine composition analysis (2-3
samples for every patient) and different details concerning these patients were
collected from our computerized system of patients’ medical records that were
our dependent resources of this study. Blood chemistries: HBA1C, FBS, KFT and
Serum Uric Acid for all patients were checked on our data system. Diagnosis of
diabetes mellitus was created by self-report within the history and current medication
use, taking into consideration that the unwellness
free was confirmed by fasting blood sugar samples below a hundred and ten
mg\dl.
All patients were given antibiotics either oral or intravenous to
avoid errors in case that there have been obvious or hidden infections before
the analysis of the urine chemistry.
Most of the information was provided within the style of a
tabulated comparative statistics; the numbers and also the percentages were
generated from the categorical data by using SPSS software version 24;
moreover, an independent t-test was used to compare mean urinary values; the
point biserial correlation was used to correlate diabetic statues with the uric
acid excretion value. P-value < 0.05 was considered statistically
significant.
An ethical
committee approval was granted by our royal medical services institution for
publication of this study.
RESULTS
After the division of the concerned
(420) participants within the previous mentioned two teams (type Π diabetics and
non-diabetics), we have a tendency to note that the ages of group-1 were
between (34 and sixty-six years);however,that the ages of group-2 were between
(21 and fifty-seven years) with insignificant P-value. In group-1 the number of
males was over females as well as in groups-2. Additionally, the number of
males was higher than females with insignificant P-value;we have atendency to
use (Table I) to match between the continual variables between
both teams.
Table I: a comparison between the continuous style of each team.
|
Variables
|
Group1(n=210)
|
Group2(n=210)
|
P
value
|
|
Ages (%)
|
34-66(50%)
|
21-57(50%)
|
0.68
|
|
Males (number\ %)
|
(143\68%)
|
(129\61.4%)
|
0.24
|
|
Females (number\ %)
|
(67\32%)
|
(81\38.6%)
|
0.43
|
According to the 24-hrs
urine collection, analytic information, the comparison between each team was created
relating to 24-hrs urine volumes, urine PH, urinary calcium and magnesium
excretion, urine net acid excretion, urine ammonium excretion, urinary citrate
excretion, urine bicarbonate excretion, and uric acid excretion. Significant P-values
were marked between both groups in relevance to the previously mentioned
variables in (Table II).
Table II: a comparison between both groups regarding 24-hours urine
collection chemistry.
|
Variables
|
Group1
|
Group2
|
P
value
|
|
24-hrs volumes (Liter/day) (mean value ± SD®)
|
(2.7±1.8)
|
(2.3±1.5)
|
0.009
|
|
Urine PH (mean value ± SD)
|
(5.45±0.42)
|
(6.23±0.38)
|
0.029
|
|
Urine calcium + magnesium excretion (mean value ± SD) (mg\day)
|
(126±22
+ 96±45)
|
(173±46
+ 211±33)
|
0.034
|
|
Urine net acid excretion(mEq\dl) (mean value ± SD)
|
(57±12)
|
(38±9)
|
0.026
|
|
Urine uric acid excretion (mean value ± SD) (mg\dl)
|
(623±257)
|
(511±134)
|
0.012
|
|
Urine citrate excretion (mEq\day) (mean value ± SD)
|
(7.9±1.8)
|
(11±3)
|
0.005
|
|
Urine Ammonium excretion (mEq\day) (mean value ± SD)
|
(38±16)
|
(30±12)
|
0.017
|
|
Urine bicarbonate excretion (mEq/day) (mean value ± SD)
|
(2.3±2.5)
|
(4.6±3.8)
|
0.042
|
SD®: standard deviation.
The Independent T-test during this study has provided us with
significant results concerning the comparison between diabetic and nondiabetic
patients regarding the 24- hours of urine collection chemistry. We have noted
that diabetic patients had significantly higher 24-h urine volumes, and
ammonium excretions and lower urinary (citrate, calcium, magnesium and
bicarbonate) excretions than non-diabetic patients (all P < 0.05). Patients
with type-2 diabetes have incontestably shown a considerably lower 24-hour
urine pH (5.45 vs. 6.23, P < 0.05) and better net acid excretion (57 vs.38
(mEq/d)) (P < 0.05) compared to non-diabetic group, respectively.
Patients with type- 2 diabetes has exhibited a significantly higher
uric acid excretion compared to non-diabetic cluster (623 mg\dl vs. 511 mg\dl.
P=0.012), respectively.
The point biserial correlation coefficient has disclosed that there
was a moderate correlation between diabetic status and the value of uric acid
excretion. (P< 0.05).
DISCUSSION
The cause of uric
acid stones are well documented. Biochemical studies on affected type2
diabetics have shown that they have several of the abnormalities. Our study has
shown that even type2 diabetics who have never formed uric acid stones have
some of the same abnormalities in the urine.
Naim Maalouf et al. reported that in type-2 diabetics, the
elevation of net acid excretion (NAE) and the decrease the ammonium buffers in
the urine will cause low urinary PH (12). These findings support our
results that incline to urolithiasis primarily uric acid stones. In contrast of
our study in relation to ammonia, Bernhard Hess detectedina review article that
insulin resistance causes low ammonium excretion , consequently a low urinary
PH which leads to uric acid stone formation (13).
In 2007,there was an article concerning uric acid nephrolithiasis
which confirmed that insulin resistance in type-2 diabetes mellitus is one of
the contributing factors that aids to uric acid stones due to the following
causative factors: hyperuricosuria, low
urinary volume and low urinary PH (14).
Regarding the mean,daily urine volumes and urine PH, N. Meydan et
al. reported that the DMT2 is a risk factor for urinary stone disease (15).
These findings were in the same side of our study.
The relationship between the acidic urine and the insulin
resistance is inversely significant. This conclusion was documented by Naim Maalouf
in 2007 by an original article which was published in the USA, Texas (16).
Despite a normouricoseuria
state, the risk of uric acid precipitation could be increased in type-2
diabetes mellitus patients because of the low urinary ammonium and PH. Nicola
Abate et al. reported that in 2004 (17).
Marry-Ann Cameron et al. found that the rise of urine ammonium in
normal individuals and type- 2 diabetic patient groups was similar;nevertheless,
in stone formers group,no changes were noted in the urine ammonium excretion. Moreover,
the main risk factor for uric acid stone formation in type-2 diabetics is low
urinary PH despite other abnormalities in urine excretion like calcium,
citrate, ammonium and magnesium excretions (18).
After the evaluation of predisposing factors of uric acid stone
formation, it was found that treatment relies on the alkalinisation of urine PH
to > 6.5 by potassium citrate to boost the solubility of uric acid and
perhaps there’s a good thing about the use of “ allopurinol” which inhibits
uric acid formationand is used to manage the hyperuricosuria side by side the
medical and surgical treatment of the stones. Therefore, in-depth comprehension
of the epidemiology as well as the Pathophysiology of uric acid stones is
essential for the treatment of these stones (19).
CONCLUSION
Type-2 diabetes
mellitus has significant influences on urine parameters which may be considered
as a precondition to nephrolithiasis mainly uric acid stones. These influences represent
high urinary volumes, low urinary PH, low citrate excrection, high net acid and
uric acid excretion in the urine. Therefore,the urine acidity will increase,and
thus the solubility of uric acid will be affected which causes stone formation.
Therefore, the management of uric acid stones contingent thorough comprehension
of Pathophysiology of those stones is crucial. So, the patients who are at risk
of uric acid stones formation should be followed up to see if they do form
stones.
REFERENCES
1.
MaryAnn
Cameron, Naim M. Maalouf, John Poindexter, et al.The
diurnal variation in urine acidification differs between normal individuals and
uric acid stone formers:Kidney International (2012) 81, 1123–1130
2.
Moe
OW. Uric acid nephrolithiasis: proton
titration of an essential molecule? Curr Opin Nephrol Hypertens 2006; 15:
366–373
3.
Maria
Giulia Battelli, Massimo Bortolotti, Letizia Polito,et al.The
role of xanthine oxidoreductase and uric acid in metabolic syndrome: BBA -
Molecular Basis of Disease 1864 (2018) 2557–2565
4.
Wild
S, Roglic G, Green A, Sicree R,et al.Global
Prevalence of Diabetes Estimates for the year 2000 and projections for
2030:Diabetes Care 27:1047–1053, 2004
5.
Daudon
M, Lacour B, Jungers P: High prevalence of uricacid calculi
in diabetic stone formers. Nephrol Dial Transplant 20: 468–469, 2005
6.
Cameron
MA, Baker LA, Maalouf NM et al. Circadian
variation in urine pH and uric acid nephrolithiasis risk. Nephrol Dial
Transplant 2007; 22:2375–2378
7.
Souto
G, Donapetry C, Calviño J, et al. Metabolic
acidosis-induced insulin resistance and cardiovascular risk. Metab Syndr Relat
Disord. 2011;9(4):247–253
8.
Abate
N, Chandalia M, Cabo-Chan AV Jr, Moe OW,Sakhaee K: The
metabolic syndrome and uric acid nephrolithiasis:Novel features of renal manifestation
of insulin resistance. Kidney Int 65: 386–392, 2004
9.
Sakhaee
K, et al. Recent advances in the pathophysiology of nephrolithiasis. Kidney
Int. 2009;75(6):585–595
10. Pak CY, Waters O, Arnold L, et al.
Mechanism for calcium urolithiasis among patients with hyperuricosuria:
supersaturation of urine with respect to monosodium urate. J Clin Invest.
1977;59(3):426–431
11. Geiss LS, Wang J, Cheng YJ, et al.
Prevalence and Incidence Trends for Diagnosed Diabetes Among Adults Aged 20 to
79 Years, United States, 1980-2012. JAMA. 2014;312(12):1218–1226
12. Maalouf NM, Cameron MA, Moe OW,et al.
Metabolic basis for low urine pH in type 2 diabetes. Clin J Am Soc Nephrol.
2010;5(7):1277–1281
13. Hess B. Metabolic syndrome, obesity and kidney stones.
Arab J Urol. 2012;10(3):258–264
14. Ngo TC, Assimos DG, et al. Uric Acid
nephrolithiasis: recent progress and future directions. Rev Urol.
2007;9(1):17–27
15. Meydan, Nezih & Barutca, Sabri & Caliskan, Sezer &
Camsari, et al. (2003). Urinary Stone Disease in Diabetes Mellitus. Scandinavian
journal of urology and nephrology. 37. 64-70
16. Maalouf, Naim & Ann Cameron, Mary & Moe, Orson &
Adams-Huet, et al. (2007). Low Urine pH: A Novel Feature of the Metabolic Syndrome.
Clinical journal of the American Society of Nephrology : CJASN. 2. 883-8
17. Nicola Abate, Manisha Chandalia, Alberto V. Cabo-Chan, et al.The
metabolic syndrome and uric acid nephrolithiasis:Novel features of renal
manifestation of insulin resistance,Kidney International,Volume 65, Issue
2,2004,Pages 386-392.
18. Ann Cameron, Mary & Maalouf, Naim & Adams-Huet, Beverley et
al. (2006). Urine Composition in Type 2 Diabetes: Predisposition to
Uric Acid Nephrolithiasis. Journal of the American Society of Nephrology :
JASN. 17. 1422-8
19. A. Abou-Elela,et al.
Epidemiology, pathophysiology, and management of uric acid urolithiasis: A
narrative review ,Journal of Advanced Research, Volume 8, Issue 5, 2017,Pages
513-527.