Chronic kidney disease (CKD) is a common disorder in felines and predominantly affects elderly cats. It is defined by persistent structural or functional renal abnormalities lasting more than three months and is characterized by progressive and irreversible decline in renal functions
(Ettinger et al., 2017). Histopathological changes include glomerulosclerosis, tubulointerstitial inflammation, tubular atrophy and interstitial fibrosis, which collectively contribute to the progression of the disease. Epidemiologic studies have reported a higher prevalence of CKD in cats, approaching nearly 50% and substantially increasing with age, reaching more than 80% in geriatric cats
(Grecu et al., 2025; Marino et al., 2014). In clinical practice, CKD is commonly classified using the international renal interest society (IRIS) staging system (stages 1-4) based on serum creatinine concentration, with further subclassification according to urine protein-to-creatinine ratio, systolic blood pressure and serum phosphate concentrations (
International Renal Interest Society, 2023). Cats with CKD may experience episodes of acute deterioration in renal functions superimposed on preexisting disease, commonly referred to as acute-on-chronic kidney disease (ACKD) (
Chen et al., 2020;
Renard et al., 2021). These episodes are frequently accompanied by sudden worsening of clinical signs, including gastrointestinal disturbances, lethargy, anorexia and dehydration. ACKD represents a diagnostic and therapeutic challenge, as it may be difficult to distinguish from acute kidney injury. Further, recovery of renal function is often incomplete, with an increased risk of accelerated CKD progression and long-term instability of renal function. Management of CKD and ACKD is largely supportive and includes fluid therapy, dietary modification, control of systemic hypertension and symptomatic management of uremia-related complications. Hospitalization and intensive medical management are often required during acute decompensation. However, current management options remain limited in their ability to prevent recurrent acute deterioration or in modifying the underlying progression of renal disease, prompting the need for adjunctive approaches aimed at supporting renal function and clinical stability. Mesenchymal stem cells (MSCs) therapy is emerging as a potential adjunctive approach for renal disease in both human and veterinary medicine (
Voga et al., 2020). MSCs are recognized for immunomodulatory, anti-inflammatory and paracrine effects supporting tissue repair and functional stabilization in chronically injured organs
(Saulnier et al., 2016; Pérez-Merino et al., 2015). In feline medicine, MSCs therapy has been suggested as a promising adjunctive approach for cats with chronic kidney disease (CKD), with reported improvements in renal function and potential to slow progression of the disease. However, earlier studies have primarily focused on its feasibility and safety with variable clinical outcomes
(Vidane et al., 2017; Quimby et al., 2011, 2013). Data regarding multiple administrations or use in the context of ACKD remain limited. The present case report describes the clinical course of a cat with CKD complicated by ACKD and its management with multiple administrations of feline amniotic membrane-derived MSCs along with conventional treatment.
Case report
The clinical evaluation and treatment described in this report were performed at Time Animal Medical Center, Daejeon, Republic of Korea, from May 2024 to May 2025.
Signalment
The animal patient was a 17-year-old spayed female Turkish Angora cat weighing 2.39 kg.
History
The feline patient was presented with recurrent vomiting occurring approximately every other day over the previous week, accompanied by progressive weight loss. According to the owner, vomiting occurred intermittently without identifiable dietary changes or other obvious triggering factors and was earlier associated with hyporexia and decreased activity. On routine laboratory monitoring approximately 18 months before presentation, the serum creatinine and symmetric dimethylarginine (SDMA) concentrations showed intermittent increases, although the values were found within reference intervals at earlier points of time. A renal-support diet (k/d early support; Hill’s pet nutrition, Topeka, KS, USA) was initiated for early renal management. A routine health evaluation approximately 6 months before presentation identified increased bilateral renal cortical echogenicity on abdominal ultrasonography, raising suspicion for chronic kidney disease (CKD). The feline patient was re-evaluated approximately 2 months before presentation for severe watery vomiting and blood testing revealed azotemia, including an increased blood urea nitrogen (BUN) and creatinine concentrations. Based on the clinical findings and laboratory results, the cat was diagnosed with international renal interest society (IRIS) stage 2 CKD and dietary management was transitioned to a renal prescription diet (k/d; Hill’s pet nutrition).
Physical examination
On physical examination, the cat exhibited mildly depressed mentation but remained alert and responsive. Rectal temperature was 38.5°C, which was within the normal range. Heart rate was 130 beats per minute and respiratory rate was 28 breaths per minute. Systolic blood pressure measured was 170 mmHg. Cardiac auscultation revealed no audible murmurs and lung sounds were unremarkable. The oral mucous membranes were dry and mildly delayed skin turgor was noted, consistent with an estimated 5% dehydration.
Diagnostic findings
Complete blood count (CBC) revealed a hematocrit of 36%, with a total white blood cell count within the reference interval and no abnormalities on differential leukocyte analysis. Serum biochemistry demonstrated azotemia, with a symmetric dimethylarginine (SDMA) concentration of 40 µg/dL, blood urea nitrogen (BUN) of 79 mg/dL and serum creatinine of 5.0 mg/dL. Hyperphosphatemia was also identified (phosphorus 8.2 mg/dL). Serum calcium concentration was 8.44 mg/dL, which was within the reference interval. Total protein, albumin and globulin concentrations were 6.95 g/dL, 2.81 g/dL and 4.1 g/dL, respectively. Blood gas analysis revealed a pH of 7.1. Urinalysis revealed a urine specific gravity of 1.010 with trace proteinuria on dipstick analysis and a urine protein-to-creatinine ratio of 0.45. Glucose was not detected in the urine. Thoracic radiographs showed a normal cardiac silhouette, with a vertebral heart score of 7.8 and no abnormalities of the pulmonary parenchyma or pulmonary vasculature. Echocardiographic examination revealed no evidence of mitral regurgitation or systolic anterior motion of the mitral valve, with normal systolic function and a diastolic left ventricular wall thickness of 5.5 mm. Abdominal ultrasonography demonstrated bilaterally small kidneys at the lower limit of the reference range, measuring 3.06 cm for the left kidney and 3.05 cm for the right kidney (reference range, 3.0-4.5 cm). The kidney-to-second lumbar vertebra (L2) length ratios were 2.0 for the left kidney and 1.9 for the right kidney (reference range, 1.9-2.6). Increased cortical echogenicity was observed in both kidneys. No other remarkable abnormalities were identified in the abdominal organs.
Therapeutic intervention
The feline patient was diagnosed with acute-on-chronic kidney disease (ACKD) basing on an acute deterioration of renal function superimposed on a pre-existing chronic kidney disease (CKD). The cat was hospitalized and a multimodal therapy was initiated which included administration of intravenous fluid for correction of dehydration, use of an antiemetic, monitoring of blood pressure and its pharmacologic management, followed by mesenchymal stem cells (MSCs) administration. Intravenous fluid therapy was initiated with normal saline at 1.5 times the maintenance rate during the initial hospitalization period to correct dehydration. After normalization of hydration status, fluid therapy was adjusted to 0.45% saline (half-normal saline) at the maintenance rate. Maropitant 1 mg/kg was administered as an antiemetic agent. For management of systemic hypertension, amlodipine (0.625 mg/cat/day) was advised. Feline amniotic membrane-derived mesenchymal stem cells were administered as an adjunctive therapy.
Feline amniotic membrane-derived MSCs were obtained from the placental amniotic membrane of a healthy donor cat. Placental tissues were collected aseptically with informed owner consent. The amniotic membrane was separated, washed with Dulbecco’s phosphate-buffered saline (DPBS) containing penicillin–streptomycin, minced into small fragments and enzymatically digested using 0.1% collagenase type I. The isolated cells were cultured in Dulbecco’s modified Eagle medium (DMEM) supplemented with 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin at 37°C in a humidified atmosphere containing 5% CO
2. Passage 3 cells were cryopreserved and stored in liquid nitrogen until clinical use. Before each administration, the cryopreserved MSCs were thawed and cultured and cell morphology and viability were assessed microscopically. The cell suspension was standardized to contain 1.5 × 10
6 viable MSCs per treatment. As premedication, chlorpheniramine 0.25 mg/kg was administered subcutaneously prior to MSCc infusion. The MSCs were diluted in 15 mL of normal saline and administered intravenously over approximately 1.5 hours. The first MSCs treatment was performed on the day of presentation and admission
i.e., Day 0. During hospitalization feline patient showed improvement in overall clinical signs and was discharged from hospital on Day 4. No clinically significant adverse effects associated with MSCs administration were observed during the treatment.
Follow-up and outcome
A second dose of MSCs was administered approximately 4 days after discharge (Day 8). Subsequent MSCs administrations were undertaken at 2-3-week intervals, according to owner and hospital scheduling, for a total of nine treatments. Renal-related parameters were monitored via blood testing at each MSCs administration. Following initiation of MSCs administration, serum BUN, creatinine and phosphorus concentrations progressively decreased and remained stable during the follow-up period (Fig 2). No delayed or cumulative adverse effects related to multiple MSCs administrations were observed. The feline patient remained clinically stable without any evidence of progression of CKD. The body weight increased from 2.39 kg to 2.8 kg and remained stable throughout the treatment period (Fig 1).
The present case describes a cat with chronic kidney disease (CKD) complicated by acute-on-chronic kidney disease (ACKD) that was managed with multimodal therapeutic approach that included multiple administrations of feline amniotic membrane-derived mesenchymal stem cells (MSCs). The patient showed sustained improvement in clinical signs and renal-related parameters during repeated MSCs therapy, without exhibiting any significant adverse effects. Although the present investigation was limited to a single case study, the findings suggest for a potential supportive role for MSCs therapy in feline CKD complicated by acute deterioration. Episodes of acute decompensation in cats with CKD were often associated with incomplete recovery and long-term renal instability. In this context, maintaining clinical stability following acute deterioration represents a key therapeutic goal, particularly in patients with limited treatment options. Mesenchymal stem cells (MSCs) administration was selected as an adjunctive treatment based on earlier proposed therapeutic rationale for renal disease
(Quimby et al., 2011). MSCs have been investigated for their potential to modulate the renal microenvironment and support stabilization during periods of renal stress. On this basis, amniotic membrane-derived MSCs were incorporated into the management strategy following conventional medical stabilization. Interpretation of the clinical course should consider the concurrent use of conventional medical management, including intravenous fluid administration, antiemetic and antihypertensive medications. These interventions would have contributed to initial stabilization during the acute phase of renal decompensation and were considered standard components of supportive care in cats with CKD complicated by acute deterioration. Therefore, the observed clinical improvement during hospitalization cannot be attributed solely to mesenchymal stem cells (MSCs) therapy. However, following stabilization with conventional treatment, repeated MSC administration was incorporated as an adjunctive approach during the follow-up period. In this context, the maintenance of clinical stability over time was observed in the setting of continued supportive care, suggesting that MSCs administration may be considered as part of a multimodal management strategy rather than as a replacement for standard established treatments. Safety was a critical consideration in the clinical application of mesenchymal stem cells (MSCs) therapy, particularly in geriatric patients with chronic kidney disease
(Song et al., 2025). In this case, multiple administrations of amniotic membrane-derived MSCs were performed a total of nine times without occurrence of any acute, delayed, or cumulative adverse effects. These observations suggest that repeated intravenous MSCs administrations were well tolerated and support the feasibility of multiple dosing protocols in feline CKD under careful clinical monitoring
(Quimby et al., 2016). Repeated MSC administration has also been investigated in other veterinary and experimental settings. Repeated applications have been reported in canine osteoarthritis and experimental cutaneous wound healing, supporting the feasibility of multiple-dose cell-based interventions
(Bhatt et al., 2021; Yaşar and Perk, 2023). More broadly, MSC-based regenerative therapy has been explored across various veterinary applications and experimental tracking following systemic administration has demonstrated the distribution of transplanted MSCs to organs including the kidney
(Gade et al., 2012; Ruan et al., 2022). This report has limitations inherent to a single-case design. The absence of a control group and the concurrent use of conventional medical management preclude determination of a causal relationship between mesenchymal stem cells (MSCs) therapy and the observed clinical course. In addition, the mechanisms underlying the potential beneficial effects of MSCs therapy could not be directly evaluated. Further, controlled clinical studies with larger sample sizes are required to assess the role of MSC therapy in cats with CKD, particularly those experiencing acute deterioration.
