BACKGROUND: Renal disease in canine leishmaniosis is of great importance owing to increased risk of mortality. In human visceral leishmaniosis, monocyte chemoattractant protein-1 (MCP-1) has been used as a marker of renal damage and inflammation. The purpose of this study was first to determine the serum MCP-1 and urinary MCP-1-to-creatinine ratio (uMCP-1/Cr) in healthy dogs and dogs with leishmaniosis at diagnosis, and second to determine whether these markers can differentiate disease severity at diagnosis.
METHODS: In total, 19 healthy seronegative dogs and 38 dogs with leishmaniosis were included in the study. Dogs with leishmaniosis were classified as LeishVet clinical staging and as International Renal Interest Society (IRIS) staging. Serum and urinary MCP-1 concentrations were measured with an enzyme-linked immunosorbent assay. A receiver operating characteristic (ROC) curve determined disease severity at diagnosis between two LeishVet groups (Stage II versus stage III and IV).
RESULTS: Dogs in Leishvet stages IIb, III, and IV had a median serum MCP-1 and uMCP-1/Cr concentration higher than healthy dogs (P < 0.0001). No statistical differences were found in serum MCP-1 and uMCP-1/Cr between dogs in LeishVet stage IIa and healthy dogs. The dogs in LeishVet stage IV had significantly higher serum MCP-1 and uMCP-1/Cr compared with the dogs in LeishVet stage IIa (P < 0.0001). Serum MCP-1 and uMCP-1 were significantly higher in dogs in IRIS stage I and II + III + IV compared with healthy dogs. Dogs stage II + III + IV of IRIS had a significantly higher serum MCP-1 compared with dogs in IRIS stage I (P < 0.0001). The area under the ROC curve for serum MCP-1 was 0.78 [95% confidence interval (CI) 0.64-0.93] and for uMCP-1/Cr it was 0.86 (95% CI, 0.74-0.99). The optimal cutoff value for serum MCP-1 and uMCP-1/Cr was 336.85 pg/ml (sensitivity of 79% and specificity of 68%) and 6.89 × 10-7 (sensitivity of 84% and specificity of 79%), respectively.
CONCLUSIONS: Serum MCP-1 and uMCP-1/Cr are increased in dogs with leishmaniosis compared with healthy dogs, suggesting the presence of inflammation and renal injury. Serum MCP-1 and uMCP-1/Cr were more elevated in the advanced stages of the disease compared with the moderate stages and, therefore, can be markers of the severity of the disease process.

Serum uremic toxins markedly increase in cats with chronic kidney disease (CKD) and have deleterious consequences. Renaltec is an oral adsorbent that binds uremic toxin precursors in the gut. In this prospective cohort study utilizing 13 purpose-bred cats with remnant kidney model-induced CKD (12 IRIS Stage 2, 1 IRIS Stage 3) eating a standardized renal diet, we aimed to assess the effect of Renaltec administration on serum indoxyl sulfate (IDS) and p-cresol sulfate (pCS) concentrations. Cats were sequentially treated with standard of care for 56 days, 500 mg Renaltec orally once daily for 56 days, and then three months later, 500 mg Renaltec orally twice daily for 56 days. Serum IDS and pCS concentrations were measured 28 and 56 days after the administration of Renaltec. Blood pressure and kidney function were measured before and 56 days after the administration of Renaltec. Significant decreases in serum IDS and pCS concentrations were observed for both once- and twice-daily dosing, particularly during the first 28 days of administration. More cats with BID dosing had clinically significant reductions in serum IDS and pCS concentrations than with SID dosing. Renaltec can reduce the serum concentrations of deleterious gut-derived uremic toxins in cats with CKD.

UNASSIGNED: X-linked agammaglobulinemia (XLA) is a humoral immunodeficiency disorder characterized by recurrent infections, severe hypogammaglobulinemia, and a deficiency of circulating B cells. While the hallmark clinical manifestations of XLA typically include the respiratory, dermatological, and gastrointestinal systems, renal involvement is infrequent. In this article, we report two cases of XLA with concurrent renal disease, supplemented with a review of documented cases.
UNASSIGNED: The two cases described involve twin brothers, both presenting with respiratory tract infections and renal manifestations. Subsequent genetic testing confirmed the diagnosis of XLA. The younger brother exhibited improvement following intravenous immunoglobulin (IVIG) therapy and anti-infection treatment. Due to financial constraints, the older brother received only anti-infection and symptomatic treatments. Seven months after discharge, the older brother developed nephritis. However, he showed improvement following IVIG treatment.
UNASSIGNED: Immune profiling and genetic testing should be considered in male children with recurrent infections to facilitate the effective diagnosis of XLA. Regular monitoring is also imperative to detect and treat immune-mediated renal diseases in patients with XLA.

Serum and urinary uromodulin are evaluated as potential biomarkers of kidney disease. The aim of our research was to select a more appropriate form of uromodulin for the diagnosis of early stages of chronic kidney disease (CKD). We also focused on the influence of age and gender in one breed on uromodulin and on the possible interbreed differences. Serum uromodulin had the lowest values in dogs younger than 2 years but no effect of gender, breed, or CKD was observed. Urinary uromodulin indexed to urinary creatinine was significantly reduced in dogs in stage 2 of CKD (p = 0.003) in contrast to uromodulin converted to urine specific gravity. Urinary uromodulin with both corrections was significantly lower in Belgian shepherds compared to German shepherds (p < 0.0001, p = 0.0054) but was not influenced by gender or age. In stage 1 of CKD, urinary uromodulin correlated with kidney disease markers SDMA (p = 0.0424, p = 0.0214) and UPC (p = 0.0050, p = 0.0024). Urinary uromodulin appears to be more associated with CKD than serum uromodulin. Further studies with a larger number of patients are needed for the suitability of urinary uromodulin as a marker of early-stage disease.

Myeloid-derived growth factor (MYDGF) is a novel secreted protein with potent antiapoptotic and tissue-repairing properties that is present in nearly 140 human tissues and cell lines, with the highest abundance in the oral epithelium and skin. Initially, MYDGF was found in bone marrow-derived monocytes and macrophages for cardioprotection and repair after myocardial infarction. Subsequent studies have shown that MYDGF plays an important role in other cardiovascular diseases (e.g., atherosclerosis and heart failure), metabolic disorders, renal disease, autoimmune/inflammatory disorders, and cancers. Although the underlying mechanisms have not been fully explored, the role of MYDGF in health and disease may involve cell apoptosis and proliferation, tissue repair and regeneration, anti-inflammation, and glycolipid metabolism regulation. In this review, we summarize the current progress in understanding the role of MYDGF in health and disease, focusing on its structure, function and mechanisms. The graphical abstract shows the current role of MYDGF in different organs and diseases (Fig. 1).

Hair cortisol concentration (HCC) and a questionnaire were used as indicators of chronic stress status and quality of life (QoL), respectively, in cats. To date, there has been limited research on the simultaneous application of both indicators in unwell cats. Our aim was to evaluate HCC and questionnaire data obtained from a healthy cat cohort (n = 61) and cat cohorts with either chronic kidney disease (CKD) (n = 78) or suspected feline infectious peritonitis (FIP) (n = 24). Furthermore, we also investigated the correlation between HCC and clinical pathological data. For this study, hair from the abdomen of cats was collected and analyzed for HCC using a commercial ELISA kit. Owners also completed a questionnaire, from which average-item-weighted-impact-scores (AWISs) were calculated. Cats with late-stage-CKD (median, HCC = 330.15 pg/mg, AWIS = -0.43) presented with a significantly higher HCC (p < 0.01) and a significantly lower AWIS (p < 0.01) than cats with early-stage-CKD (HCC = 183.56 pg/mg, AWIS = 1.08). Similarly, there were significant differences in both HCC (p < 0.001) and AWIS (p < 0.001) between cats with suspected FIP (HCC = 896.27 pg/mg, AWIS = -1.97) and healthy cats (HCC = 181.24 pg/mg, AWIS = 1.24). The degree of consistency between the HCC results and the questionnaire results reminds us that the severity of a chronic disease or the presence of a life-threatening disease can significantly increase stress and thus can affect the QoL of cats.

Hepatitis C virus still represents a major cause of morbidity and mortality worldwide. In Peru, two national practice guidelines for the management of this infection were published more than 5 years ago; however, the latest breakthroughs in the treatment make it necessary to update these guidelines. We reviewed the most recent recommendations of the international guidelines and compared them with the current Peruvian guidelines. We found major differences, such as the use of Glecaprevir/Pibrentasvir as a first-line therapy, which is contemplated in the World Health Organization guideline, and recommended by American and European guidelines, but is not considered in the Peruvian guidelines. Another crucial difference lies in the management of patients with chronic kidney disease, who are treated nowadays with a variety of direct-acting antivirals, with no restrictions on the use of Sofosbuvir-based regimens in first-world countries, an approach that has not been adopted in Peru. We believe that standardization of the recommendations of the Peruvian guidelines is imperative, including the new therapeutic strategies that have emerged in recent years. We also suggest conducting a cost effectiveness analysis in the Peruvian context to allow for the implementation of new antivirals, and to achieve a better control of hepatitis C in the country.

UNASSIGNED: Urine testing as a routine screening programme, abnormal test results can be suggestive to clinicians but can sometimes be overlooked, and the establishment of a diagnostic model can better assist clinicians in identifying potential problems. BLD (blood), LEU (leukocyte), PRO (protein) and GLU (glucose) are the four most important parameters in urine testing, and the accuracy of their results is a key concern for clinicians, so it is essential to verify the accuracy of their results. In this study, we evaluated the analytical and clinical performance of Mindray\'s automatic urine dry chemistry analyzer, the UA-5600 (Hereinafter referred to as the (UA-5600), and the test strips configured with the instrument, and developed a machine-learning (ML) model for kidney disease screening from the results of 11 parameters output from the UA-5600 with the aim of detecting abnormal urine test results.
UNASSIGNED: Urine samples from outpatients and inpatients at The First Affiliated Hospital of Sun Yat-sen University were collected from August to September 2022 to evaluate the performance of the Mindray UA-5600 dry chemistry analyzer and test strips. The evaluation of the UA-5600 and its test strips focused on the agreement of the urine BLD and LEU readings with the RBC (red blood cell) and WBC (white blood cell) counts obtained by the Mindray EH-2090 urine formed element analyzer. We also compared the PRO and GLU readings with the results of the Mindray BS-2800M biochemistry analyzer. Urine samples from outpatients and inpatients were retrospectively analysed and grouped according to LIS diagnosis. Additionally, eight ML models for kidney disease screening were developed using 11 parameters measured by the UA-5600. And the model was validated by the validation set.
UNASSIGNED: The UA-5600 had an 89.55% concordance rate for BLD and a 91.04% concordance rate for LEU compared to the EH-2090 analyzer. When benchmarked against the BS-2800M, the concordance rates for PRO and GLU were 94.14% and 95.20%, respectively. A total of 1,691 samples were used for the construction of the ML models, of which 346 patients (135 males and 211 females, age range: 18 to 98 years) diagnosed with renal disease, and 1,345 patients (397 males and 948 females, age range: 18 to 92 years) with non-renal disease diagnosed with other conditions. Notably, the Naïve Bayes (NB) model, which was built from the UA-5600 parameters, demonstrated superior predictive capabilities for renal disease, with an area under the receiver operating characteristic curve of 0.9470, a sensitivity of 0.7767, and a specificity of 0.9457.
UNASSIGNED: The Mindray UA-5600 demonstrates robust detection abilities for both BLD and LEU, and its results for PRO and GLU align closely with those obtained from the chemistry analyzer. The NB model has a good screening ability and shows promise as an effective screening tool.

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We report the case of a patient who exhibits a concurrent diagnosis of type 1 diabetes mellitus, Gitelman syndrome and Cacci-Ricci disease. A 27-year-old male patient was diagnosed with Gitelman syndrome at the age of 3 years. Fourteen years later, he developed an autoantibody-negative type 1 diabetes mellitus. Cacci-Ricci\'s disease was revealed by terminal hematuria and considered in view of the appearance found on the computed tomography (CT) scan. The finger-prick blood glucose level was 6 g/dl with no acetonuria. Creatinine clearance was 60 ml/min. Thyroid function tests were normal. Calcium, phosphorus and parathormone (PTH) levels were normal. Discussion: Gitelman syndrome is a rare disorder. The association between Gitelman syndrome and type 1 diabetes mellitus has been reported in the literature in two patients. Authors have investigated the association between Gitelman syndrome and type 2 diabetes mellitus. Several pathophysiological explanations have been put forward. Cacci-ricci disease is a rare, benign congenital anomaly. No association between type 1 diabetes mellitus, Gitelman syndrome and Cacci-Ricci disease has been reported in the literature. To our knowledge, this is the first case described in the literature.