This study was conducted in accordance with institutional guidelines for the use of animals in research and was reviewed and approved by the Ethics Committee of Kasetsart University, Thailand, under approval number ACKU-65-VET-077. The study involved client-owned cats presented to the Kasetsart University Veterinary Teaching Hospital, Kamphaeng Saen, and was based on retrospective evaluation of medical records, renal ultrasonographic findings, hematological and biochemical data, and PKD1 genotyping results obtained during routine clinical assessment. Written informed consent was obtained from all owners before inclusion of their animals in the study. Sample collection was limited to procedures performed as part of standard veterinary diagnostic care, including peripheral blood sampling and abdominal ultrasonography, and no additional invasive procedures were undertaken solely for research purposes. All examinations and sample handling were performed by qualified veterinary personnel in accordance with accepted standards of animal welfare and good clinical practice. Confidentiality of owner and animal information was maintained throughout the study, and all data were analyzed anonymously.

This retrospective, single-center observational study was conducted at the Animal Teaching Hospital, Kamphaeng Saen, Faculty of Veterinary Medicine, Kasetsart University, Thailand. Medical records and biological samples were reviewed from cats presented between January 2024 and September 2025. The hospital functions as a referral center for companion animals in central Thailand, providing routine preventive care, diagnostic imaging, and advanced clinical services. The study workflow comprised case identification and eligibility screening, clinical and ultrasonographic assessment, laboratory and molecular analyses, and statistical evaluation.

A total of 28 client-owned cats (mean age 5.34 ± 2.25 years, body weight 3.50 ± 0.85 kg) were enrolled through convenience sampling based on the availability of complete clinical records and biological samples. Written informed consent was obtained from all owners before inclusion. Cats aged ≥1 year were eligible for enrollment. Exclusion criteria included concurrent chronic systemic diseases known to influence inflammatory or renal biomarkers, such as chronic kidney disease, diabetes mellitus, epilepsy, or other severe systemic illnesses, as determined by medical history, physical examination, and laboratory findings. All cats underwent standardized clinical evaluation, including assessment of sex, breed, age, body weight, and medical history. Routine diagnostic procedures included abdominal ultrasonography and blood profile analysis. Approximately 1 mL of blood was collected aseptically from peripheral veins and processed immediately for complete blood count (CBC) and serum biochemistry using standard hospital protocols.

Renal ultrasonography was performed by an experienced veterinary clinician using a cardiac-capable ultrasound system equipped with a high-frequency transducer. Cats were examined in right- and left-lateral recumbency following routine abdominal imaging protocols. Still images and cine loops were digitally archived for subsequent analysis. Renal cysts were defined as well-circumscribed, anechoic structures with distal acoustic enhancement. Cats presenting with more than two renal cysts were classified as having PKD according to previously published criteria [14]. All measurements were obtained from recorded images, as illustrated in Figure 1.

Genomic DNA was extracted from frozen whole-blood samples using a commercial DNA extraction kit according to the manufacturer’s instructions. Detection of the PKD1 mutation was performed using polymerase chain reaction (PCR) as previously described. The primer sequences were 5'-AGCCTTCAGCAAGAAGCCA-3' (forward) and 5'-CAAACTTGACCTTGGAGGAGC-3' (reverse). PCR amplification followed standardized cycling conditions reported in earlier studies investigating feline PKD mutations.

PCR products were purified using a commercial PCR purification kit before sequencing. Purified amplicons were subjected to Sanger sequencing using the same primer pairs as those used for PCR. Sequence chromatograms were analyzed and aligned using BioEdit software, and polymorphisms were identified by comparison with reference PKD1 sequences.

Serum samples were centrifuged and stored under appropriate conditions until analysis. Hematological data obtained from the CBC were used to calculate inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and PLR, following established veterinary methods. Serum C-reactive protein (CRP) concentrations were measured using a validated assay according to the manufacturer’s protocol. These biomarkers were selected to assess subclinical inflammatory status in cats with PKD.

Data were assessed for normality before analysis and are presented as mean ± SEM. Continuous variables were compared using Student’s t-test or one-way analysis of variance, as appropriate. Pearson’s correlation analysis was used to evaluate associations among renal imaging parameters, genetic status, and inflammatory biomarkers. A p-value < 0.05 was considered statistically significant. Statistical analyses were performed using GraphPad Prism software (version 10.0) in accordance with standard biostatistical guidelines.

All cats included in the study were clinically stable at the time of evaluation. None exhibited overt clinical signs commonly associated with advanced renal disease, including anorexia, weight loss, vomiting, polyuria, polydipsia, lethargy, or dehydration. Physical examination parameters, including body condition score, hydration status, heart rate, respiratory rate, and blood pressure, were within acceptable age- and breed-specific reference ranges. Importantly, no cats were classified as azotemic, and none fulfilled the diagnostic criteria for chronic kidney disease at enrollment. No mortality events occurred during the study period, and no cats required euthanasia or were lost to follow-up because of renal-related complications. As this was a retrospective, clinically oriented study involving client-owned animals, postmortem examination and histopathological evaluation were not available and were therefore not included in the analysis.

The most prevalent breeds among the enrolled cats were Scottish Fold (n = 9, 32.14%), Persian (n = 7, 25%), domestic shorthair (n = 4, 14.28%), and mixed breeds (n = 8, 28.58%). Based on renal ultrasonographic findings and PKD1 genotyping, cats were categorized into three groups: Group 1, healthy control cats without renal cysts and without PKD1 mutation; Group 2, cats with polycystic kidneys and a wild-type PKD1 genotype identified by ultrasonography; and Group 3, cats with polycystic kidneys carrying a heterozygous PKD1 mutation. Group allocation and baseline characteristics are summarized in Table 1.

Renal ultrasonographic findings for all cats are presented in Table 2. Cats in Groups 2 and 3 exhibited multiple, well-defined anechoic renal cysts with distal acoustic enhancement, consistent with polycystic kidney morphology. Cysts were bilaterally distributed in affected cats and varied in size and number. Significant differences in kidney length and height were observed among groups, reflecting structural renal remodeling in cats with cystic disease. In contrast, the kidney-to-aortic diameter ratio did not differ significantly among groups, indicating consistent normalization for body size across populations. Representative ultrasonographic images are shown in Figure 1.

Hematological and biochemical parameters for all cats (n = 28) are summarized in Table 3. To minimize confounding effects, cats with pre-existing hematologic disorders, diagnosed chronic kidney disease, or a history of anticoagulant therapy were excluded before analysis. Mean concentrations of creatinine, blood urea nitrogen, and SDMA did not differ significantly among groups (p > 0.05), indicating preserved renal excretory function across all study populations. Similarly, total plasma protein and CRP concentrations showed no statistically significant intergroup differences.

In contrast, inflammatory cell ratios demonstrated notable trends. NLR tended to be higher in Group 2 (9.17 ± 8.13) compared with Group 1 (3.82 ± 1.77) and Group 3 (4.09 ± 1.80), approaching statistical significance (p = 0.0508). MLR showed a similar borderline difference (p = 0.0534), with higher values observed in Group 3 (0.28 ± 0.13). PLR was numerically elevated in Group 3 (258.19 ± 4.00), although this difference did not reach statistical significance.

Correlation matrixes are illustrated in Figures 2 and 3. In clinically healthy cats (Group 1), moderate positive correlations were observed among inflammatory ratios, particularly between NLR and PLR (r = 0.86) and between NLR and MLR (r = 0.62). However, inflammatory biomarkers showed weak or negligible associations with renal biochemical indices and kidney morphometric measurements. In contrast, cats with renal cysts (Groups 2 and 3 combined) demonstrated markedly stronger correlations. NLR correlated strongly with PLR (r = 0.94) and showed positive associations with blood urea nitrogen (r = 0.71), creatinine (r = 0.63), SDMA (r = 0.62), and kidney morphometrics (length r = 0.82, height r = 0.75). PLR also correlated positively with blood urea nitrogen (r = 0.81) and creatinine (r = 0.61). These findings indicate an emerging link between low-grade systemic inflammation and structural renal changes in cats with cystic kidney disease, even in the absence of overt renal dysfunction.

No gross pathological specimens, histopathological slides, or postmortem findings were available, as all cats were alive, clinically stable, and managed under standard clinical care. Consequently, renal histopathology and downstream molecular pathway analyses were beyond the scope of this retrospective study. Molecular investigation was limited to PKD1 genotyping, and intracellular signaling pathways or molecular mechanisms related to cystogenesis were not assessed.

This study examined the relationship between systemic inflammatory indices, renal structure, renal function, and PKD1 genotype in cats with renal cystic disease. The principal finding is that systemic inflammatory activation is detectable in cats with cystic kidney changes despite preservation of conventional renal biomarkers, and that this inflammatory signal is more pronounced in cats carrying a PKD1 mutation. These findings support the concept that inflammation precedes overt renal dysfunction in feline PKD and parallels structural renal remodeling.

Previous studies on feline PKD have focused largely on genetic diagnosis and imaging characteristics, with limited emphasis on systemic inflammatory responses during early disease stages. Consistent with earlier reports, cats in the present study showed normal creatinine, blood urea nitrogen, and SDMA concentrations, indicating preserved renal excretory function in early or compensated PKD [15, 16]. Similar observations have been reported in both feline and human PKD, where substantial nephron loss may occur before biochemical markers exceed reference ranges.

Despite stable renal biomarkers, NLR, MLR, and PLR demonstrated distinct group-related trends, suggesting early immune activation. The elevated NLR observed in cats with cystic kidneys and wild-type PKD1 genotype may reflect acute or intermediate inflammatory responses associated with mechanical cyst expansion and epithelial injury. Comparable increases in NLR have been described in human autosomal dominant PKD and experimental renal cystic models, where neutrophil recruitment precedes interstitial fibrosis [17, 18].

In contrast, the higher MLR observed in cats carrying a PKD1 mutation suggests a shift toward monocyte- and macrophage-driven chronic inflammation, a recognized feature of progressive PKD. Macrophage infiltration is a hallmark of cystic kidneys and contributes to fibroblast activation, extracellular matrix deposition, and cyst enlargement [19]. These findings indicate that distinct inflammatory profiles may characterize different stages of disease progression or genetic backgrounds in PKD.

CRP concentrations did not differ significantly among groups, in agreement with previous feline studies reporting limited sensitivity of CRP in chronic, low-grade inflammatory conditions, particularly renal disease. Unlike acute inflammatory disorders, PKD progression is insidious, and systemic CRP responses may remain subdued until advanced stages.

The numerical increase in PLR observed in cats with PKD1 mutations suggests a potential role for platelet activation in chronic renal inflammation. Platelets are increasingly recognized as active contributors to renal fibrogenesis through the release of pro-inflammatory and pro-fibrotic mediators, including platelet-derived growth factor and transforming growth factor-β [18, 19]. Although PLR differences did not reach statistical significance, this trend supports its possible utility as a supplementary indicator of disease activity.

Correlation analyses demonstrated a progression from weak associations in healthy cats to strong, multivariate correlations in cats with cystic kidneys and PKD1 mutations. In non-cystic cats, inflammatory and renal parameters were largely independent, reflecting physiological homeostasis. In contrast, cats with renal cysts exhibited strong positive correlations between inflammatory indices, kidney size, and renal biochemical markers, even though these values remained within reference ranges.

These findings parallel observations in human PKD, where kidney enlargement correlates more closely with disease progression than early biochemical markers [20, 21]. The strong associations between inflammatory indices and renal morphometrics in PKD1-mutated cats suggest that kidney enlargement may promote systemic inflammation through mechanisms such as tubular stretch, epithelial stress, and cytokine release.

The amplified correlations observed in cats carrying PKD1 mutations underscore the central role of genetic disruption in PKD pathogenesis. The PKD1 gene encodes polycystin-1, which is essential for renal tubular epithelial mechanosensation and calcium signaling. Loss of polycystin-1 function results in dysregulated intracellular calcium homeostasis, mitochondrial dysfunction, oxidative stress, and activation of inflammatory transcription factors, including NF-κB [22, 23].

The observed relationships between inflammatory markers, renal function indices, and blood pressure in PKD1-mutated cats support a model in which a systemic inflammatory–renal–vascular response is initiated by genetic mutation. Hypertension, which correlated with inflammatory and renal parameters in this study, is a recognized consequence of PKD progression and contributes to further nephron injury and cyst expansion [24]. Collectively, these findings indicate that systemic inflammation is an integral component of PKD pathophysiology rather than merely a secondary consequence of renal dysfunction.

The results suggest that hematological inflammatory ratios, particularly NLR and MLR, may serve as accessible and cost-effective tools for identifying early inflammatory activity in cats with renal cysts, even before the development of azotemia. Integration of these indices with ultrasonography and genetic testing may enhance risk stratification, disease monitoring, and early intervention strategies in feline PKD.

This study has several limitations. The sample size was relatively small, which may limit statistical power and generalizability. As a retrospective, single-center study, environmental influences, dietary factors, and subclinical comorbidities could not be fully controlled. Because all cats were alive and clinically stable, histopathological confirmation and postmortem evaluation were not available, precluding direct assessment of renal fibrosis, inflammatory infiltrates, and cyst wall pathology. Molecular analyses were limited to PKD1 genotyping, and downstream signaling pathways involved in cystogenesis and inflammation were not directly evaluated. Finally, the duration of follow-up was limited. Longitudinal studies with larger cohorts, repeated inflammatory assessments, advanced imaging, and integration of molecular and histopathological data are needed to validate inflammatory ratios as prognostic biomarkers in feline PKD.