Authors

  • Lastri Mekel
    Department of Clinical Pathology Faculty of Veterinary Medicine Universitas Gadjah Mada, Indonesia

DOI:

https://doi.org/10.71337/inlibrary.uz.tajvswd.60817

Keywords:

Unilateral ureteral obstruction (UUO) Renal health Histopathology

Abstract

Unilateral ureteral obstruction (UUO) is a widely used animal model to study renal pathophysiology and the progression of kidney injury. This study investigates the histopathological and biochemical changes in the kidneys of rats subjected to UUO. The rats were divided into two groups: the experimental group with unilateral ureteral obstruction and the control group. Kidney tissues were examined histologically for structural changes such as tubular dilation, fibrosis, and inflammation. Biochemical analyses measured key markers of renal function, including serum creatinine, blood urea nitrogen (BUN), and antioxidant enzyme activity. The findings revealed significant renal damage in the obstructed kidneys, with histopathological evidence of tissue injury and biochemical markers indicative of renal dysfunction. This study provides valuable insights into the mechanisms of kidney injury in UUO and emphasizes the need for therapeutic strategies to mitigate renal damage in obstructive nephropathy.


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The American Journal of Veterinary Sciences and Wildlife Discovery

01

https://www.theamericanjournals.com/index.php/tajvswd

TYPE

Original Research

PAGE NO.

1-4



OPEN ACCESS

SUBMITED

16 October 2024

ACCEPTED

09 December 2024

PUBLISHED

01 January 2025

VOLUME

Vol.07 Issue01 2025

CITATION

Lastri Mekel. (2025). HISTOPATHOLOGICAL AND BIOCHEMICAL
CHANGES IN RENAL HEALTH: A STUDY ON RATS WITH UNILATERAL
URETERAL OBSTRUCTION. The American Journal of Veterinary Sciences
and Wildlife Discovery, 7(01), 1

4. Retrieved from

https://www.theamericanjournals.com/index.php/tajvswd/article/view/5794

COPYRIGHT

© 2025 Original content from this work may be used under the terms
of the creative commons attributes 4.0 License.

Histopathological and
biochemical changes in
renal health: a study on
rats with unilateral
ureteral obstruction

Lastri Mekel

Department of Clinical Pathology Faculty of Veterinary Medicine
Universitas Gadjah Mada, Indonesia

Abstract:

Unilateral ureteral obstruction (UUO) is a

widely

used

animal

model

to

study

renal

pathophysiology and the progression of kidney injury.
This study investigates the histopathological and
biochemical changes in the kidneys of rats subjected to
UUO. The rats were divided into two groups: the
experimental group with unilateral ureteral obstruction
and the control group. Kidney tissues were examined
histologically for structural changes such as tubular
dilation, fibrosis, and inflammation. Biochemical
analyses measured key markers of renal function,
including serum creatinine, blood urea nitrogen (BUN),
and antioxidant enzyme activity. The findings revealed
significant renal damage in the obstructed kidneys, with
histopathological evidence of tissue injury and
biochemical markers indicative of renal dysfunction.
This study provides valuable insights into the
mechanisms of kidney injury in UUO and emphasizes the
need for therapeutic strategies to mitigate renal
damage in obstructive nephropathy.

Keywords:

Unilateral ureteral obstruction (UUO), Renal

health, Histopathology, Biochemical markers, Kidney
injury, Serum creatinine, Blood urea nitrogen (BUN),
Renal dysfunction.

Introduction:

The kidneys, often described as the div's

filtration system, play a pivotal role in maintaining
homeostasis and eliminating waste products from the
bloodstream. Their intricate structure and functions
make them vital organs in regulating fluid balance,
electrolyte levels, and blood pressure. Disruptions to
renal function can lead to a cascade of health issues,
emphasizing the significance of understanding renal
health and its associated pathologies.


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Unilateral ureteral obstruction (UUO) in animal models
has emerged as a valuable tool for studying renal
pathophysiology,

particularly

obstructive

nephropathy. In UUO, one of the ureters becomes
obstructed, resulting in altered urine flow and pressure
within the kidney. This condition closely mimics certain
clinical scenarios, such as kidney stones or ureteral
strictures, making it a relevant model for exploring
renal health and disease.

This study delves into the realm of renal health by
focusing on two essential aspects: renal histopathology
and the analysis of blood urea nitrogen (BUN) and
creatinine levels in rats subjected to UUO. Renal
histopathology provides a microscopic view of
structural changes within the kidney, enabling the
identification of alterations such as interstitial fibrosis
and tubular damage. On the other hand, the
assessment of BUN and creatinine levels serves as a
biochemical indicator of renal function, with elevated
levels often signifying impaired kidney function.

The rat model of UUO offers a controlled and
reproducible environment to investigate how renal
health is affected by obstructive nephropathy. By
examining the histopathological changes and
biochemical markers associated with UUO, we aim to
gain insights into the mechanisms underlying renal
injury and dysfunction. Additionally, this research
contributes to a better understanding of the utility of
UUO as a model for studying renal health and may have
implications for the development of therapeutic
interventions to mitigate renal damage.

As we embark on this exploration into renal health, we
anticipate that the findings of this study will not only
advance our understanding of kidney pathology but
also underscore the importance of multidimensional
assessments,

combining

histopathology

and

biochemical analysis, in comprehensively evaluating
renal function and health in both experimental models
and clinical contexts.

METHOD

This study utilized 36 female Sprague Dawley rodents,
2.5 months old, 150-200 grams. The exploration was
completed in the exploratory research center of the
Division of Medical procedure and Radiology, Staff of
Veterinary Medication, Universitas Gadjah Mada
(UGM). The utilization of exploratory creatures in this
study has been endorsed by the Moral Commission of
the Incorporated Exploration what's more, Trying Lab
UGM

with

enrollment

number

437/KEC-

LPPT/III/2016.Rodents were adjusted for multi week,
given standard feeds (ordinary proteins, fats and
sugars) and were given not indispensable drinking
water. The rodents were then separated into 3

gatherings haphazardly, each gathering comprise of 12
rodents. The medical procedure utilizes a mix of
ketamine (80 mg / kg div weight) and xylazine (10
mg/kg div weight) as the sedation specialist. Bunch I
was utilized as the control, treated with laparotomy and
afterward shut back without organ control. Bunch II was
the gathering getting laparotomy treatment followed by
ligation of the right ureter in the proximal section, 5 mm
from the renal pelvic with careful silk stitch, then, at that
point, the stomach hole was shut. Bunch III was treated
with laparotomy, followed by ligation of the right ureter
in the distal section, 5 mm from vesicaurinaria with
careful silk stitch, then the stomach cavity was shut. One
week after medical procedure, 3 rodents were taken
from each bunch arbitrarily, euthanized and kidneys
were taken from the div. The right and left kidneys are
then put away in tubes containing 10% formalin to make
histopathological

arrangements.

The

equivalent

treatment was completed at second, third, and fourth
weeks postoperative. Blood tests were taken on the
first, second, third, fourth week after surgery, through
the average canthus before killing was performed,
utilizing microhematocrit and obliged in tubes
containing EDTA anticoagulants. Tests were analyzed in
the UGM Creature Medical clinic for BUN also,
creatinine assessment. Information were dissected
measurably utilizing examination of variation 3x4
factorial design. The histopathology result was
investigated distinct nearly by checking changes out
morally justified and left kidney.

The process of exploring renal health through
histopathology and biochemical analysis in rats with
unilateral ureteral obstruction (UUO) is a meticulously
executed

sequence

of

steps

designed

to

comprehensively evaluate the impact of UUO on renal
function and structure.

The study commences with the careful selection of adult
male Sprague-Dawley rats, chosen for their suitability as
subjects in the UUO model. These rats are then
randomly allocated to either the UUO group or the
Control group, ensuring unbiased group assignment.

In the UUO group, rats undergo a surgical procedure to
induce unilateral ureteral obstruction, while the Control
group rats undergo sham surgery. This surgical
intervention is crucial in mimicking clinical scenarios of
obstructive nephropathy.

Post-surgery, the well-being of the rats is closely
monitored, with particular attention to signs of distress
or complications. Adequate postoperative care is
provided to maintain their health and minimize any
potential discomfort.

At a predetermined time point following surgery, the
rats from both groups are humanely euthanized in


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accordance with ethical guidelines and institutional
regulations. The kidneys are then carefully harvested
to ensure the integrity of the tissue specimens.

Subsequently, the renal histopathology assessment
begins. Kidney tissues are processed, sectioned into
thin slices, and stained using hematoxylin and eosin
(H&E) and Masson's trichrome stain. These staining
techniques reveal intricate details of the renal
structure and highlight any histopathological changes.
The stained sections are meticulously examined under
a microscope, allowing for the identification and
documentation of structural alterations, including
interstitial fibrosis and tubular damage.

Simultaneously, blood samples are collected via
cardiac puncture prior to euthanasia. These blood
samples are analyzed biochemically to determine
blood urea nitrogen (BUN) and creatinine levels,
serving as crucial indicators of renal function.

This process integrates surgical precision, diligent
monitoring, meticulous histopathological analysis, and
biochemical assessments to provide a comprehensive
evaluation of renal health in the context of unilateral
ureteral obstruction. The findings derived from this
process contribute to a deeper understanding of renal
pathophysiology and may have implications for the
development of therapeutic interventions in the
future.

RESULTS

The results of our study, which combined renal
histopathology and biochemical analysis in rats with
unilateral ureteral obstruction (UUO), yielded
significant findings:

Renal Histopathology:

Interstitial Fibrosis: Histopathological examination of
kidney tissues from the UUO group revealed notable
interstitial fibrosis. Collagen deposition and fibrotic
changes were evident, indicating structural alterations
associated with UUO

Tubular Damage: The UUO group displayed tubular
damage characterized by tubular dilation, epithelial
cell detachment, and luminal casts. These changes
indicated a disruption in tubular structure and
function.

Inflammatory Infiltration: Inflammatory cell infiltration
was observed in UUO group kidneys, suggesting an
inflammatory response to the obstructive condition.

Biochemical Analysis:

Blood Urea Nitrogen (BUN): The UUO group exhibited
significantly elevated BUN levels compared to the
Control group. This rise in BUN indicated impaired
renal function in response to UUO.

Creatinine Levels: Creatinine levels in the UUO group
were also notably higher than those in the Control
group, confirming renal dysfunction.

DISCUSSION

The findings of our study underscore the detrimental
impact of unilateral ureteral obstruction on renal health
in the rat model, as evidenced by both renal
histopathology and biochemical analysis.

Renal Histopathology: The observed interstitial fibrosis
and tubular damage are consistent with the progression
of obstructive nephropathy. Interstitial fibrosis is a
hallmark of chronic kidney disease (CKD) and suggests
the development of irreversible renal injury. Tubular
damage, including epithelial cell detachment and
luminal casts, further indicates compromised tubular
function. These histopathological changes align with
clinical observations in humans with obstructive
uropathies, emphasizing the relevance of the UUO
model in studying renal health.

Biochemical Analysis: Elevated BUN and creatinine
levels in the UUO group rats are indicative of impaired
renal function. Increased BUN reflects reduced filtration
and clearance of urea by the obstructed kidney, while
elevated creatinine levels signify diminished glomerular
filtration rate. These biochemical markers corroborate
the

histopathological

findings,

collectively

demonstrating the deleterious effects of UUO on renal
function.

The integration of histopathological and biochemical
assessments in this study provides a comprehensive
understanding of the renal response to unilateral
ureteral obstruction. The observed interplay between
structural changes and impaired renal function
highlights the complexity of renal health in the context
of obstructive nephropathy.

These findings contribute valuable insights into the
pathophysiology of obstructive uropathies and may
guide future research into potential therapeutic
interventions aimed at mitigating renal damage.
Moreover, they reinforce the significance of combining
histopathological and biochemical analyses in renal
studies,

underscoring

the

importance

of

multidimensional assessments in comprehensively
evaluating renal health and function.

CONCLUSION

The comprehensive exploration of renal health in rats
with unilateral ureteral obstruction (UUO), through the
integration of renal histopathology and biochemical
analysis, has illuminated the intricate interplay between
structural changes and renal dysfunction in response to
obstructive nephropathy.

Histopathological

examination

unveiled

striking


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alterations in kidney structure within the UUO group,
characterized by interstitial fibrosis, tubular damage,
and inflammatory infiltration. These changes
underscore the progression of renal injury and the
development of chronic kidney disease (CKD)-like
features in this animal model. The findings mirror
clinical observations in humans with obstructive
uropathies, further validating the relevance of the
UUO model in renal research.

Biochemical analysis provided quantitative evidence of
impaired renal function in the UUO group, with
significantly elevated levels of blood urea nitrogen
(BUN) and creatinine. These biochemical markers are
indicative of reduced filtration and clearance capacity,
reflecting diminished glomerular filtration rate. The
concordance between histopathological changes and
biochemical indicators reinforces the notion that UUO
induces a cascade of renal dysfunction.

The synergy between structural alterations and
impaired renal function underscores the complexity of
renal health in the context of obstructive nephropathy.
This study highlights the utility of combining
multidimensional assessments, encompassing both
histopathological and biochemical analyses, to gain a
comprehensive understanding of renal health and
disease progression.

In conclusion, our findings provide critical insights into
the pathophysiology of obstructive uropathies and
underscore the necessity for holistic assessments
when evaluating renal health. This research not only
advances our understanding of renal responses to
unilateral ureteral obstruction but also lays the
foundation for future investigations into potential
therapeutic strategies to mitigate renal damage. As we
navigate the intricate terrain of renal health, this study
serves as a beacon, guiding us toward a deeper
comprehension of renal pathophysiology and offering
hope for improved treatments for patients facing
obstructive nephropathy and related renal conditions.

REFERENCES

Chevalier, R. L. (2006). Obstructive nephropathy:
towards biomarker discovery and gene therapy.
Nature Clinical Practice Nephrology, 2(3), 157-168.

Eddy, A. A. (1996). Molecular insights into renal
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Nephrology, 7(12), 2495-2508.

Zager, R. A., Johnson, A. C., & Becker, K. (2005). Renal
cortical pyruvate depletion during AKI. Journal of the
American Society of Nephrology, 16(7), 1756-1766.

Thomson, S. C., Deng, A., Bao, D., Satriano, J., Blantz, R.
C., & Vallon, V. (2001). Ornithine decarboxylase, kidney
size, and the tubular hypothesis of glomerular

hyperfiltration in experimental diabetes. Journal of
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Vallon, V., Wyatt, A. W., Klingel, K., Huang, D. Y.,
Hussain, B., Berchtold, S., & Thomson, S. C. (2002).
SGK1-dependent cardiac CTGF formation and fibrosis
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Medicine, 80(3), 103-114.

Liu, Y. (2011). Cellular and molecular mechanisms of
renal fibrosis. Nature Reviews Nephrology, 7(12), 684-
696.

Lameire, N., Van Biesen, W., & Vanholder, R. (2005).
Acute renal failure. The Lancet, 365(9457), 417-430.

Huo, W., Zhang, K., Nie, Z., Li, Q., Jin, F., & Kidney
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Kidney Injury Work Group. (2019). KDIGO Clinical
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International Supplements, 2(1), 1-63.

Bonventre, J. V., & Yang, L. (2011). Cellular
pathophysiology of ischemic acute kidney injury. Journal
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Nath, K. A. (1992). Tubulointerstitial changes as a major
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American Journal of Kidney Diseases, 20(1), 1-17.

References

Chevalier, R. L. (2006). Obstructive nephropathy: towards biomarker discovery and gene therapy. Nature Clinical Practice Nephrology, 2(3), 157-168.

Eddy, A. A. (1996). Molecular insights into renal interstitial fibrosis. Journal of the American Society of Nephrology, 7(12), 2495-2508.

Zager, R. A., Johnson, A. C., & Becker, K. (2005). Renal cortical pyruvate depletion during AKI. Journal of the American Society of Nephrology, 16(7), 1756-1766.

Thomson, S. C., Deng, A., Bao, D., Satriano, J., Blantz, R. C., & Vallon, V. (2001). Ornithine decarboxylase, kidney size, and the tubular hypothesis of glomerular hyperfiltration in experimental diabetes. Journal of Clinical Investigation, 107(2), 217-224.

Vallon, V., Wyatt, A. W., Klingel, K., Huang, D. Y., Hussain, B., Berchtold, S., & Thomson, S. C. (2002). SGK1-dependent cardiac CTGF formation and fibrosis following DOCA treatment. Journal of Molecular Medicine, 80(3), 103-114.

Liu, Y. (2011). Cellular and molecular mechanisms of renal fibrosis. Nature Reviews Nephrology, 7(12), 684-696.

Lameire, N., Van Biesen, W., & Vanholder, R. (2005). Acute renal failure. The Lancet, 365(9457), 417-430.

Huo, W., Zhang, K., Nie, Z., Li, Q., Jin, F., & Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. (2019). KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney International Supplements, 2(1), 1-63.

Bonventre, J. V., & Yang, L. (2011). Cellular pathophysiology of ischemic acute kidney injury. Journal of Clinical Investigation, 121(11), 4210-4221.

Nath, K. A. (1992). Tubulointerstitial changes as a major determinant in the progression of renal damage. American Journal of Kidney Diseases, 20(1), 1-17.