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Abstract Background Options for treatment of diabetes mellitus in cats are limited to insulin injections and monitoring for hypoglycemia. Hypothesis Once daily sodium‐glucose cotransporter‐2 inhibitor velagliflozin PO is noninferior to insulin injections. Animals Client‐owned diabetic cats (127 safety; 116 efficacy assessment). Methods Prospective, randomized (1 mg/kg velagliflozin), positive controlled (titrated Caninsulin), open label, noninferiority field trial, comparing number of cats with treatment success in ≥1 clinical variable and ≥1 glycemic variable (margin Δ: 15%) on Day 45; secondary endpoints included glycemic and clinical assessments during 91 days. Results On Day 45, 29/54 (54%) velagliflozin‐treated cats and 26/62 (42%) Caninsulin‐treated cats showed treatment success, demonstrating noninferiority (difference −11.8%; upper 1‐sided 97.5% confidence interval, −∞ to 6.3%). By Day 91, quality of life (QoL), polyuria, and polydipsia had improved in 81%, 54% and 61% (velagliflozin); on blood glucose (BG) curves, mean BG was

Background: Options for treatment of diabetes mellitus in cats are limited to insulin injections and monitoring for hypoglycemia. Hypothesis: Once daily sodium‐glucose cotransporter‐2 inhibitor velagliflozin PO is noninferior to insulin injections. Animals: Client‐owned diabetic cats (127 safety; 116 efficacy assessment). Methods: Prospective, randomized (1 mg/kg velagliflozin), positive controlled (titrated Caninsulin), open label, noninferiority field trial, comparing number of cats with treatment success in ≥1 clinical variable and ≥1 glycemic variable (margin Δ: 15%) on Day 45; secondary endpoints included glycemic and clinical assessments during 91 days. Results: On Day 45, 29/54 (54%) velagliflozin‐treated cats and 26/62 (42%) Caninsulin‐treated cats showed treatment success, demonstrating noninferiority (difference −11.8%; upper 1‐sided 97.5% confidence interval, −∞ to 6.3%). By Day 91, quality of life (QoL), polyuria, and polydipsia had improved in 81%, 54% and 61% (velagliflozin); on blood glucose (BG) curves, mean BG was <252 mg/dL in 42/54 (78%; velagliflozin) and 37/62 (60%; Caninsulin); minimum BG was <162 mg/dL in 41/54 (76%; velagliflozin) and 41/62 (66%; Caninsulin); serum fructosamine was <450 μmol/L in 41/54 (76%; velagliflozin) and 38/62 (61%; Caninsulin). Velagliflozin's most frequent adverse events were loose feces/diarrhea (n = 23/61, 38%), positive urine culture (n = 19/61, 31%), and nonclinical hypoglycemia (BG <63 mg/dL; n = 8/61, 13%); Caninsulin's: clinical and nonclinical hypoglycemia (n = 35/66, 53%), positive urine culture (n = 18/66, 27%), and loose feces/diarrhea (n = 10/66, 15%). Diabetic ketoacidosis occurred in 4/61 (7%; velagliflozin) and 0/66 (Caninsulin). Conclusions and Clinical Importance: Once daily oral administration of velagliflozin was noninferior to insulin injections, showed good QoL and glycemia without clinical hypoglycemia. [ABSTRACT FROM AUTHOR]

In this longitudinal observational study, we measured urinary glucose concentration, body composition and volume status (bioimpedance spectroscopy) and plasma renin and aldosterone concentrations in n = 22 kidney transplant recipients (KTRs) initiating on SGLT2I at baseline (BL), and after 1 week and 1, 3, and 6months. Estimated glomerular filtration rate (eGFR) decreased by -2mL/min/1.73 m² (IQR -10--0) after 1 week and remained stable thereafter. Urinary glucose concentration was 10 (3--24) g/g creatinine after 1 week and correlated with eGFR (r² = 0.273; p = 0.057). SGLT2I did not affect HbA1c, fasting blood glucose, body weight, fat or lean mass. SGLT2I decreased fluid overload dependent on baseline overhydration (OH, r² = 0.54, p = 0.0003) without occurrence of dehydration. Plasma aldosterone increased at day 7, while plasma renin did not change significantly. In conclusion, SGLT2I corrected fluid overload in patients with elevated overhydration at baseline, while in euvolemic KTRs fluid status remained stable without reduction of body water below the reference range, thus promoting the safety of SGLT2I therapy in patients following kidney transplantation. Glucosuria, together with effects of SGLT2I on blood glucose control and body weight, is attenuated in KTRs dependent on eGFR. [ABSTRACT FROM AUTHOR]

Aim: To examine the impact of increased hepatic glucose production (HGP) on the decrease in plasma glucose concentration caused by empagliflozin in individuals living with diabetes and in nondiabetic individuals. Methods: A total of 36 individuals living with diabetes and 34 nondiabetic individuals were randomized to receive, in double‐blind fashion, empagliflozin or matching placebo in a 2:1 treatment ratio. Following an overnight fast, HGP was measured with 3‐3H‐glucose infusion before, at the start of, and 3 months after therapy with empagliflozin. Results: On Day 1 of empagliflozin administration, the increase in urinary glucose excretion (UGE) in individuals with normal glucose tolerance was smaller than in those with impaired glucose tolerance and those living with diabetes, and was accompanied by an increase in HGP in all three groups. The amount of glucose returned to the systemic circulation as a result of the increase in HGP was smaller than that excreted by the kidney during the first 3 h after empagliflozin administration, resulting in a decrease in fasting plasma glucose (FPG) concentration. After 3 h, the increase in HGP was in excess of UGE, leading to a small increase in plasma glucose concentration, which reached a new steady state. After 12 weeks, the amount of glucose returned to the circulation due to the empagliflozin‐induced increase in HGP was comparable with that excreted by the kidney in all three groups. Conclusion: The balance between UGE and increase in HGP immediately after sodium‐glucose cotransporter‐2 (SGLT2) inhibition determined the magnitude of decrease in FPG and the new steady state which was achieved. After 12 weeks, the increase in HGP caused by empagliflozin closely matched the amount of glucose excreted by the kidneys; thus, FPG level remained stable despite the continuous urinary excretion of glucose caused by SGLT2 inhibition. [ABSTRACT FROM AUTHOR]

Hydroxyhydroquinone (HHQ) is an oxidative component produced by roasting coffee beans and has been reported to generate relatively large amounts of reactive oxygen species (ROS). In this study, we used senescence-accelerated mouse prone 8 (SAMP8) mice to determine whether HHQ consumption increases oxidative-stress-induced injury, because in SAMP8 mice, the activity of 8-oxoguanine DNA glycosylase 1, which repairs oxidative modifications in DNA, is decreased. The results showed that two out of twelve (16.7%) HHQ-treated mice presented polyuria and glucosuria around 2 months after the start of treatment, indicating that HHQ may act as a mutagen against SAMP8 mice, which is sensitive to oxidative damage. No abnormalities were observed in the chlorogenic acid (coffee polyphenol, CPP)-treated group. The concentration of hydrogen peroxide in the serum of SAMP8 mice was significantly higher than that in SAMR1 (senescence-resistant) control mice, and the concentration was further increased in the HHQ-treated group. CPP, when coexisting with HHQ at the rate contained in roasted coffee, decreased the amount of hydrogen peroxide in the serum of SAMP8 mice. Although CPP can act both oxidatively and antioxidatively as a polyphenol, CPP acts more antioxidatively when coexisting with HHQ. Thus, the oxidative effect of HHQ was shown to be counteracted by CPP. [ABSTRACT FROM AUTHOR]

Our recent development of a wireless humidity sensor system embedded in incontinence products enables new sensor applications to diagnose and supervise geriatric diseases (i.e., age-related diabetes mellitus type II). The measurement of glucose in urine, so-called glucosuria, is an early indicator for an incipient diabetes mellitus disease, whose symptoms are often age-related but misjudged. In this paper, an incontinence glucose sensor is printed with biocompatible ink and Prussian blue as an electron mediator on foil and functionalized with immobilized glucose oxidase. Inkjet printing of multiple layers of Nafion prevents large interference substances from diffusing into the measuring electrode and allows precise adjustment of the linear working range, which is significantly different from blood glucose measurement. Performance tests show the potential to detect minimum glucose values and store the sensor over a prolonged period at room temperature. The printed glucose sensor can be embedded into the absorber material of incontinence products, where capillary forces transport the urine analyte to the detection area. An attached readout module with an integrated potentiostat measures the glucose concentration in urine, which is transmitted wirelessly with incontinence events and stored in a cloud service for further analysis by medical staff and care workers.

Fanconi syndrome is a disorder of the proximal renal tubule. Recently, advanced genetic analysis technology has revealed that several genes cause familial Fanconi syndrome. We identified a family with autosomal dominant Fanconi syndrome and chronic kidney disease with a novel glycine amidinotransferase (GATM) variant. Case 1 was a 57-year-old Japanese woman. Her father and two siblings had Fanconi syndrome or chronic kidney disease. She presented to our hospital at the age of 34 years with recurrent glucosuria. Her height and weight were 151 cm and 46.6 kg, respectively. Laboratory tests showed glucosuria, hypophosphatemia, hypouricemia, and normal renal function. Her serum creatinine level gradually increased over the following next two decades, and she developed end-stage renal disease. Case 2, the daughter of Case 1, was a 26-year-old woman. Her height and weight were 151 cm and 37.5 kg, respectively. Glucosuria was detected at the age of 13 years, which led to a referral to our hospital. Urinalysis showed low-molecular-weight proteinuria. She was diagnosed with Fanconi syndrome. At the age of 26 years, she had glucosuria, low-molecular-weight proteinuria, hypouricemia, and normal renal function. Genetic testing of both cases revealed a novel missense variant in GATM. The heterozygous missense variants in GATM have been reported to cause familial Fanconi syndrome, which manifests early in life and progresses to renal glomerular failure by mid-adulthood. The novel GATM variant detected in our cases was suspected to be associated with the development of Fanconi syndrome. GATM variants should be tested in patients with idiopathic Fanconi syndrome. [ABSTRACT FROM AUTHOR]

Case summary: A 3-year-old male neutered Sphynx cat was referred for history of chronically increased liver enzymes and lower urinary tract signs that were first reported when the cat was 5 months old. Urine metabolic profile revealed increased amino aciduria and glucosuria despite normoglycemia, suggesting Fanconi syndrome. Urine sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a banding pattern suggestive of primary tubular damage. Serial blood work showed non-regenerative normocytic normochromic anemia, persistently elevated liver enzymes, worsening azotemia and progressive hyperchloremic metabolic acidosis. Ultrasound revealed irregular kidneys and bilaterally hyperechoic cortices and medullae with a loss of normal corticomedullary distinction. Laparoscopic kidney biopsy revealed a moderate-to-severe chronic interstitial fibrosis with chronic lymphoplasmacytic inflammation, tubular degeneration and atrophy, mild glomerulosclerosis and mild large vascular amyloidosis. Tubular epithelial cell karyomegaly was multifocally evident throughout the kidney. The liver had moderate diffuse zone 1 hepatocellular atrophy, periportal fibrosis, biliary hyperplasia, mild perisinusoidal amyloidosis and hepatocyte karyomegaly in zones 2 and 3. The patient continued to decline and developed polyuria, polydipsia, lethargy and hyporexia irrespective of rigorous management, which failed to curtail the progressive anemia and azotemia. The patient was euthanized 8 months from the onset of clinical signs. Relevance and novel information: Fanconi syndrome in cats is a rare condition, with most reports occurring secondary to chlorambucil treatment. This is the first known case of Fanconi syndrome occurring with concurrent hepatorenal epithelial karyomegaly in a young Sphynx cat. [ABSTRACT FROM AUTHOR]

Our recent development of a wireless humidity sensor system embedded in incontinence products enables new sensor applications to diagnose and supervise geriatric diseases (i.e., age-related diabetes mellitus type II). The measurement of glucose in urine, so-called glucosuria, is an early indicator for an incipient diabetes mellitus disease, whose symptoms are often age-related but misjudged. In this paper, an incontinence glucose sensor is printed with biocompatible ink and Prussian blue as an electron mediator on foil and functionalized with immobilized glucose oxidase. Inkjet printing of multiple layers of Nafion prevents large interference substances from diffusing into the measuring electrode and allows precise adjustment of the linear working range, which is significantly different from blood glucose measurement. Performance tests show the potential to detect minimum glucose values and store the sensor over a prolonged period at room temperature. The printed glucose sensor can be embedded into the absorber material of incontinence products, where capillary forces transport the urine analyte to the detection area. An attached readout module with an integrated potentiostat measures the glucose concentration in urine, which is transmitted wirelessly with incontinence events and stored in a cloud service for further analysis by medical staff and care workers. [ABSTRACT FROM AUTHOR]

The sodium–glucose cotransporter 2 (SGLT2) mainly carries out glucose reabsorption in the kidney. Familial renal glycosuria, which is a mutation of SGLT2, is known to excrete glucose in the urine, but blood glucose levels are almost normal. Therefore, SGLT2 inhibitors are attracting attention as a new therapeutic drug for diabetes, which is increasing worldwide. In fact, SGLT2 inhibitors not only suppress hyperglycemia but also reduce renal, heart, and cardiovascular diseases. However, whether long-term SGLT2 inhibition is completely harmless requires further investigation. In this context, mice with mutations in SGLT2 have been generated and detailed studies are being conducted, e.g., the SGLT2−/− mouse, Sweet Pee mouse, Jimbee mouse, and SAMP10-ΔSglt2 mouse. Biological changes associated with SGLT2 mutations have been reported in these model mice, suggesting that SGLT2 is not only responsible for sugar reabsorption but is also related to other functions, such as bone metabolism, longevity, and cognitive functions. In this review, we present the characteristics of these mutant mice. Moreover, because the relationship between diabetes and Alzheimer's disease has been discussed, we examined the relationship between changes in glucose homeostasis and the amyloid precursor protein in SGLT2 mutant mice. [ABSTRACT FROM AUTHOR]

Renal Fanconi syndrome (RFS) affects the proximal tubular resorption in the nephrons. This causes excessive loss of key solutes through the urine. In a canine patient, we successfully managed the renal tubular acidosis and proteinuria caused by RFS via transplantation of canine adipose tissue-derived mesenchymal stem cells (cAT-MSCs). cAT-MSCs were administered ten times at intervals of 2-4 weeks. The post-therapy check-up revealed that the cAT-MSC treatment improved the renal tubular acidosis and proteinuria. Hence, a cAT-MSC transplant may be considered as an adjuvant therapy in veterinary medicine to initiate and maintain relief of RFS-induced acidosis and proteinuria.

Approximately 20–40% of all diabetic patients experience chronic kidney disease, which is related to higher mortality (cardiovascular and all-cause). A large body of evidence suggests that renal hypoxia is one of the main forces that drives diabetic kidney disease, both in its early and advanced stages. It promotes inflammation, generation of intrarenal collagen, capillary rarefaction and eventually accumulation of extracellular matrix that destroys normal renal architecture. SGLT2 inhibitors are unquestionably a practice-changing drug class and a valuable weapon for patients with type 2 diabetes and chronic kidney disease. They have achieved several beneficial kidney effects after targeting multiple and interrelated signaling pathways, including renal hypoxia, independent of their antihyperglycemic activities. This manuscript discusses the pathophysiological concepts that underly their possible effects on modulating renal hypoxia. It also comprehensively investigates both preclinical and clinical studies that explored the possible role of SGLT2 inhibitors in this setting, so as to achieve long-term renoprotective benefits. [ABSTRACT FROM AUTHOR]

The urinary bladder is markedly enlarged in the type 1 diabetes mellitus model of streptozotocin-injected rats, whichmay contribute to the frequent diabetic uropathy. Much less data exists for models of type 2 diabetes. Diabetic polyuria has been proposed as the pathophysiological mechanism behind bladder enlargement. Therefore, we explored such a relationship across nine distinct rodent models of diabetes including seven models of type 2 diabetes/obesity by collecting data on bladder weight and blood glucose from 16 studies with 2-8 arms each; some studies included arms with various diets and/or pharmacological treatments. Data were analysed for bladder enlargement and for correlations between bladder weight on the one and glucose levels on the other hand. Our data confirm major bladder enlargement in streptozotocin rats and minor if any enlargement in fructose-fed rats, db/db mice and mice on a high-fat diet; enlargement was present in some of five not reported previously models. Bladder weight was correlated with blood glucose as a proxy for diabetic polyuria within some but not other models, but correlations were moderate to weak except for RIP-LCMV mice (r2 of pooled data from all studies 0.0621). Insulin levels also failed to correlate to a meaningful extent. Various diets and medications (elafibranor, empagliflozin, linagliptin, semaglutide) had heterogeneous effects on bladder weight that often did not match their effects on glucose levels. We conclude that the presence and extent of bladder enlargement vary markedly across diabetes models, particularly type 2 diabetes models; our data do not support the idea that bladder enlargement is primarily driven by glucose levels/glucosuria. [ABSTRACT FROM AUTHOR]

The urinary bladder is markedly enlarged in the type 1 diabetes mellitus model of streptozotocin-injected rats, which may contribute to the frequent diabetic uropathy. Much less data exists for models of type 2 diabetes. Diabetic polyuria has been proposed as the pathophysiological mechanism behind bladder enlargement. Therefore, we explored such a relationship across nine distinct rodent models of diabetes including seven models of type 2 diabetes/obesity by collecting data on bladder weight and blood glucose from 16 studies with 2–8 arms each; some studies included arms with various diets and/or pharmacological treatments. Data were analysed for bladder enlargement and for correlations between bladder weight on the one and glucose levels on the other hand. Our data confirm major bladder enlargement in streptozotocin rats and minor if any enlargement in fructose-fed rats, db/db mice and mice on a high-fat diet; enlargement was present in some of five not reported previously models. Bladder weight was correlated with blood glucose as a proxy for diabetic polyuria within some but not other models, but correlations were moderate to weak except for RIP-LCMV mice (r2 of pooled data from all studies 0.0621). Insulin levels also failed to correlate to a meaningful extent. Various diets and medications (elafibranor, empagliflozin, linagliptin, semaglutide) had heterogeneous effects on bladder weight that often did not match their effects on glucose levels. We conclude that the presence and extent of bladder enlargement vary markedly across diabetes models, particularly type 2 diabetes models; our data do not support the idea that bladder enlargement is primarily driven by glucose levels/glucosuria.

Abstract Aims/Introduction Glucosuria is a representative symptom in diabetes patients with poor glycemic control and in those treated with sodium–glucose cotransporter 2 inhibitors. Renal threshold levels of glucose excretion are known to vary among individuals, but factors contributing to glucosuria are not well characterized. The present study aimed to clarify clinical and genetic determinants of glucosuria in individuals with diabetes mellitus. Materials and Methods The 24‐h urinary glucose excretion was measured in 135 hospitalized patients on admission, with continuous measurement for five consecutive days in 75 patients. Genetic and clinical factors contributing to glucosuria were studied. As a genetic factor, SLC5A2 polymorphism was genotyped. A total of 476 participants (266 participants with type 2 diabetes and 210 healthy controls) were additionally genotyped for the association study of SLC5A2 with type 2 diabetes. A meta‐analysis was carried out with the present study and previous association studies. Results Multiple regression analysis showed that the independent variables of average blood glucose (β = 0.41, P = 1.4 × 10−7), estimated glomerular filtration rate (β = 0.28, P = 6.0 × 10−5), sex (β = 0.28, P = 5.7 × 10−5) and SLC5A2 rs9934336 polymorphism (β = 0.17, P = 0.02) were significantly correlated with urinary glucose excretion. The frequency of the A allele of rs9934336 tended to be lower in participants with type 2 diabetes than in controls (odds ratio 0.78, 95% confidence interval 0.53–1.13, not significant), and meta‐analysis showed a significant association between the A allele and type 2 diabetes (summary odds ratio for minor allele [A] 0.86, 95% confidence interval 0.78–0.94, P

Background: Diabetes mellitus type 2 has been linked to pancreatic islet amyloid deposition in humans and nonhuman primates. The authors hypothesized that diabetic primates would have significant differences in pathology than non‐diabetic groups. Methods: This retrospective study used histopathology and immunohistochemistry to characterize and compare pancreatic islet amyloidosis in 58 diabetic and non‐diabetic rhesus macaque (RM) and sooty mangabeys (SM). Results: The pancreatic tissues from diabetic RM and SM showed higher histopathology scores for islet amyloid deposit distribution, severity, and calcification deposits compared to their respective non‐diabetic cohorts. Further, these tissues from RM and SM with amyloid deposits showed immunoreactivity to insulin, glucagon, islet amyloid polypeptide, serum amyloid P, and glucagon‐like peptide 1. Conclusions: Histopathology results showed that the defined amyloid characteristics are associated with clinical diabetes in both species. The immunohistochemistry results collectively suggest differences in pancreatic hormones and islet amyloid components among both species and diabetic status. [ABSTRACT FROM AUTHOR]

Renal Fanconi syndrome (RFS) affects the proximal tubular resorption in the nephrons. This causes excessive loss of key solutes through the urine. In a canine patient, we successfully managed the renal tubular acidosis and proteinuria caused by RFS via transplantation of canine adipose tissue-derived mesenchymal stem cells (cAT-MSCs). cAT-MSCs were administered ten times at intervals of 2–4 weeks. The post-therapy check-up revealed that the cAT-MSC treatment improved the renal tubular acidosis and proteinuria. Hence, a cAT-MSC transplant may be considered as an adjuvant therapy in veterinary medicine to initiate and maintain relief of RFS-induced acidosis and proteinuria. [ABSTRACT FROM AUTHOR]

Background and Aim: Sodium-glucose cotransporter (SGLT)-2 inhibitors are novel anti-diabetic medications with potential beneficial effects on cardiovascular and renal outcomes, metabolic parameters, and body weight. In addition to the beneficial effects on renal functions, including estimated glomerular filtration rate and reduction in proteinuria, recent studies have investigated the potential role of SGLT-2 inhibitor therapy on nephrolithiasis development. Nephrolithiasis, a condition affecting almost 10% of the general population at least once during a lifetime, is a common disorder with considerable risk for acute and chronic kidney injury and relatively few effective therapeutic options., Materials and Methods: We have performed a literature search through multiple databases, including PubMed, Ovid/Medline, Web of Science, Scopus, and Cochrane Library. We have followed the systematic review and meta-analysis guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses.We have included a total of 11 635 698 patients who experienced nephrolithiasis from six clinical trials to conduct this meta-analysis study. In the pooled analysis, nephrolithiasis occurred in 1,27% of patients from the SGLT2i group (n = 739 197), compared to 1,56% of patients (n = 10 896 501) from the control arm (active control, placebo or no therapy)., Results: We have included a total of 11 635 698 participants who experienced nephrolithiasis from a total of six clinical studies with nephrolithiasis rates of 1,27% in the SGLT2i group (n = 739 197), compared to 1,56% in the control arm (n = 10 896 501). SGLT-2 inhibitor therapy has been associated with a lower risk for nephrolithiasis compared to placebo (OR 0.61, 95% CI, 0.53-0.70, p < 0.00001) or active therapy such as glucagon-like peptide 1 and dipeptidyl peptidase-IV inhibitors (OR 0.66, 95% CI, 0.47-0.93, p = 0.02)., Conclusion: We have demonstrated a lower risk of nephrolithiasis risk with SGLT-2 inhibitor therapy compared to placebo or active control. Potential underlying mechanisms include osmotic diuresis leading to a reduction in the concentration of lithogenic substances, anti-inflammatory and anti-fibrotic effects, and an increase in urine pH. There is a clear need for future large-scale randomized clinical trials evaluating such associations for better understanding., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Abstract Background Gene coding mutations found in sodium glucose co-transporters (SGLTs) are known to cause renal glucosuria. SGLT2 inhibitors have recently been shown to be effective hypoglycemic agents as well as possessing cardiovascular and renal protective properties. These beneficial effects have to some extent, been attributed to weight loss and reduced blood pressure. The aim of the current study was to evaluate the prevalence of renal glucosuria amongst a large cohort of Israeli adolescents and to investigate whether renal glucosuria is associated with lower body weight and lower blood pressure values. Methods Medical and socio-demographic data were collected from the Israeli Defense Force’s conscription center’s database. A cross-sectional study to evaluate the association between conscripts diagnosed as overweight [BMI percentiles of ≥ 85 and

Aims/Introduction: Glucosuria is a representative symptom in diabetes patients with poor glycemic control and in those treated with sodium–glucose cotransporter 2 inhibitors. Renal threshold levels of glucose excretion are known to vary among individuals, but factors contributing to glucosuria are not well characterized. The present study aimed to clarify clinical and genetic determinants of glucosuria in individuals with diabetes mellitus. Materials and Methods: The 24‐h urinary glucose excretion was measured in 135 hospitalized patients on admission, with continuous measurement for five consecutive days in 75 patients. Genetic and clinical factors contributing to glucosuria were studied. As a genetic factor, SLC5A2 polymorphism was genotyped. A total of 476 participants (266 participants with type 2 diabetes and 210 healthy controls) were additionally genotyped for the association study of SLC5A2 with type 2 diabetes. A meta‐analysis was carried out with the present study and previous association studies. Results: Multiple regression analysis showed that the independent variables of average blood glucose (β = 0.41, P = 1.4 × 10−7), estimated glomerular filtration rate (β = 0.28, P = 6.0 × 10−5), sex (β = 0.28, P = 5.7 × 10−5) and SLC5A2 rs9934336 polymorphism (β = 0.17, P = 0.02) were significantly correlated with urinary glucose excretion. The frequency of the A allele of rs9934336 tended to be lower in participants with type 2 diabetes than in controls (odds ratio 0.78, 95% confidence interval 0.53–1.13, not significant), and meta‐analysis showed a significant association between the A allele and type 2 diabetes (summary odds ratio for minor allele [A] 0.86, 95% confidence interval 0.78–0.94, P < 0.002). Conclusions: Blood glucose, estimated glomerular filtration rate, sex and SLC5A2 polymorphism were independent determinants of glucosuria in diabetes mellitus. [ABSTRACT FROM AUTHOR]

Objectives: Prednisolone is a commonly used drug in cats and potential adverse effects include hyperglycaemia and diabetes mellitus. The aims of this study were to evaluate the frequency and investigate potential predisposing risk factors for the development of prednisolone-induced diabetes mellitus (PIDM) in cats. Methods: The electronic records of a tertiary referral centre were searched for cats receiving prednisolone at a starting dose of ⩾1.9 mg/kg/day, for >3 weeks and with follow-up data available for >3 months between January 2007 and July 2019. One hundred and forty-three cats were included in the study. Results: Of the 143 cats, 14 cats (9.7%) were diagnosed with PIDM. Twelve out of 14 cats (85.7%) developed diabetes within 3 months of the initiation of therapy. Conclusions and relevance: Cats requiring high-dose prednisolone therapy should be closely monitored over the first 3 months of therapy for the development of PIDM. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (DM2) is a chronic condition that affects more than 400 million individuals worldwide. In DM2 patients, an appropriate glycemic control slows the onset and delays the progression of all its micro and macrovascular complications. Even though there are several glucose-lowering drugs, only approximately half of patients achieve glycemic control, while undesirable adverse effects (e.g., low serum glucose) normally affect treatment. Therefore, there is a need for new types of treatments. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have just been developed for treating DM2. Renal hyperfiltration as a marker of increased intraglomerular pressure in diabetic patients, and the role of renin–angiotensin–aldosterone system (RAAS) in this phenomenon have been studied. Nevertheless, RAAS blockade does not completely reduce hyperfiltration or diabetic renal damage. In this sense, the contribution of renal tubular factors to the hyperfiltration state, including sodium–glucose cotransporter (SGLT), has been currently studied. SGLT2i reduce proximal tubular sodium reabsorption, therefore increasing distal sodium delivery to the macula densa, causing tubule-glomerular feedback activation, afferent vasoconstriction, and reduced hyperfiltration in animal models. In humans, SGLT2i was recently shown to reduce hyperfiltration in normotensive, normoalbuminuric patients suffering from type 1 diabetes mellitus. In DM2 clinical trials, SGLT2 is associated with significant hyperfiltration and albuminuria reduction. The aim of this article is to compile the information regarding SGLT2i drugs, emphasizing its mechanism of renal repercussion. [ABSTRACT FROM AUTHOR]

Purpose Familial renal glucosuria (FRG, OMIM #233100) is a rare but relatively benign genetic condition characterized by persistent isolated glucosuria with a normal blood glucose level. We report three additional SLC5A2 mutations and examine their phenotypic and genetic characteristics in a Korean FRG cohort. We also reviewed the literature and summarized the genotypes of all Korean patients with FRG. Methods A genetic analysis was conducted by directly sequencing all 14 exons of the SLC5A2 gene and their flanking regions in six unrelated Korean children with FRG and their family members. Novel non-synonymous single-nucleotide polymorphisms were identified and compared with known mutations that are repeatedly detected in the Korean population. Results We found two novel mutations [c.274G>A (G92S) and c.1168C>T (L390F)] and one known [c.1382G>A (S461N)] mutation in each family and one recurrent mutation [c.1346G>A (G449D) (rs768392222)] in two pedigrees. The recurrent G449D was predicted to be “possibly damaging,” with a score of 0.883 in Polyphen-2, while G92S, L390F, and S461N were predicted to be “probably damaging,” with scores of 1.000, 0.999, and 0.996, respectively. Conclusions Two novel, one previously reported, and one recurrent mutation were identified in six Korean FRG pedigrees as causative mutations of renal glucosuria. Sequence variations in the SLC5A2 gene were frequently detected in children with persistent isolated glucosuria. A long-term follow-up of this FRG cohort is needed to understand how these specific SGLT2 mutations impair kidney function and energy homeostasis.

Aims: Diabetes mellitus is a progressive, chronic, systemic, metabolic disease that must be managed effectively. Its prevalence is increasing rapidly. We investigated whether urologists' awareness and recognition of glucosuria contributed to the diagnosis of diabetes and regulation of blood glucose. Methods: A total of 39,053 patients were retrospectively evaluated between January 2018 and February 2019. Of them, 16,211 had undergone urinalysis for varied reasons. Glucosuria was semi-quantitatively measured as (+), (++), (+++), and (++++). Patients were assessed in terms of whether they had been referred to endocrinology or internal medicine departments within the 15 days and the presence/absence of a previous or new diagnosis of diabetes mellitus by measuring blood glucose and HgbA1c levels. Results: Glucosuria was detected in 665 patients (4.1%), of whom 495 were included in the study. 417 (84.2%) had been previously diagnosed with diabetes mellitus, and 56 (11.3%) newly received a diabetes mellitus diagnosis. Blood glucose and HbA1c values were normal in 22 (4.4%) patients with glucosuria. HgbA1c value was determined as 7 or above in 381 (91.3%) of 417 cases with a previous diabetes mellitus diagnosis. Conclusion: Referring all patients detected to have glucosuria in the spot urine test at any time regardless of fasting/non-fasting to the relevant departments can contribute to the diagnosis and treatment of diabetes mellitus disease. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The glucosuria induced by sodium–glucose cotransporter 2 (SGLT2) inhibition stimulates endogenous (hepatic) glucose production (EGP), blunting the decline in HbA1c. We hypothesised that, in response to glucosuria, a renal signal is generated and stimulates EGP. To examine the effect of acute administration of SGLT2 inhibitors on EGP, we studied non-diabetic individuals who had undergone renal transplant with and without removal of native kidneys. Methods: This was a parallel, randomised, double-blind, placebo-controlled, single-centre study, designed to evaluate the effect of a single dose of dapagliflozin or placebo on EGP determined by stable-tracer technique. We recruited non-diabetic individuals who were 30–65 years old, with a BMI of 25–35 kg/m2 and stable body weight (±2 kg) over the preceding 3 months, and HbA1c <42 mmol/mol (6.0%). Participants had undergone renal transplant with and without removal of native kidneys and were on a stable dose of immunosuppressive medications. Participants received a single dose of dapagliflozin 10 mg or placebo on two separate days, at a 5- to 14-day interval, according to randomisation performed by our hospital pharmacy, which provided dapagliflozin and matching placebo, packaged in bulk bottles that were sequentially numbered. Both participants and investigators were blinded to group assignment. Results: Twenty non-diabetic renal transplant patients (ten with residual native kidneys, ten with bilateral nephrectomy) participated in the study. Dapagliflozin induced greater glucosuria in individuals with residual native kidneys vs nephrectomised individuals (8.6 ± 1.1 vs 5.5 ± 0.5 g/6 h; p = 0.02; data not shown). During the 6 h study period, plasma glucose decreased only slightly and similarly in both groups, with no difference compared with placebo (data not shown). Following administration of placebo, there was a progressive time-related decline in EGP that was similar in both nephrectomised individuals and individuals with residual native kidneys. Following dapagliflozin administration, EGP declined in both groups, but the differences between the decrement in EGP with dapagliflozin and placebo in the group with bilateral nephrectomy (Δ = 1.11 ± 0.72 μmol min−1 kg−1) was significantly lower (p = 0.03) than in the residual native kidney group (Δ = 2.56 ± 0.33 μmol min−1 kg−1). In the population treated with dapagliflozin, urinary glucose excretion was correlated with EGP (r = 0.34, p < 0.05). Plasma insulin, C-peptide, glucagon, prehepatic insulin:glucagon ratio, lactate, alanine and pyruvate concentrations were similar following placebo and dapagliflozin treatment. β-Hydroxybutyrate increased with dapagliflozin treatment in the residual native kidney group, while a small increase was observed only at 360 min in the nephrectomy group. Plasma adrenaline (epinephrine) did not change after dapagliflozin and placebo treatment in either group. Following dapagliflozin administration, plasma noradrenaline (norepinephrine) increased slightly in the residual native kidney group and decreased in the nephrectomy group. Conclusions/interpretation: In nephrectomised individuals, the hepatic compensatory response to acute SGLT2 inhibitor-induced glucosuria was attenuated, as compared with individuals with residual native kidneys, suggesting that SGLT2 inhibitor-mediated stimulation of hepatic glucose production via efferent renal nerves occurs in an attempt to compensate for the urinary glucose loss (i.e. a renal–hepatic axis). Trial registration: ClinicalTrials.gov NCT03168295 Funding: This protocol was supported by Qatar National Research Fund (QNRF) Award No. NPRP 8-311-3-062 and NIH grant DK024092-38. Graphical abstract [ABSTRACT FROM AUTHOR]

Diabetes is a metabolic disorder characterized by hyperglycemia and is associated with several comorbidities and complications. Genital infection is one such complication that is often associated with diabetes mellitus (DM). Even though abnormalities in immune system, high urine glucose, and bladder dysfunction are important contributors for the increased risk of genitourinary symptoms, yet the possible role of pharmacologically induced glucosuria cannot be completely overlooked in such patients. There are various classes of medications to control blood glucose levels. A new therapeutic option to manage hyperglycemia is to increase renal glucose excretion by inhibiting sodium-glucose cotransporter-2 (SGLT2) glucose transport proteins. SGLT2 inhibitors (SGLT2i) represent a novel class of oral antidiabetic drugs which are associated with drug-induced glucosuria. Currently, canagliflozin, dapagliflozin, and empagliflozin are the three SGLT2i approved for therapy in Type 2 DM (T2DM). Safety studies with these three SGLT2i have reported events of mild-moderate genital infections in patients on SGLT2i therapy. However, most of the reported infections responded to standard treatment. Apart from SGLT2i, factors including personal hygiene, menopause, and circumcision might have a possible role in reported events of genital infections among T2DM patients on SGLT2i therapy. The present review identifies the occurrence of genital infections in diabetic patients on SGLT2i therapy, factors affecting the incidence of genital infections, and management strategies in patients with T2DM on SGLT2i therapy.

Abstract Most of the filtered glucose is reabsorbed in the early proximal tubule by the sodium‐glucose cotransporter SGLT2. The glycosuric effect of the SGLT2 inhibitor ipragliflozin is linked to a diuretic and natriuretic effect that activates compensatory increases in fluid and food intake to stabilize body fluid volume (BFV). However, the compensatory mechanisms that are activated on the level of renal tubules remain unclear. Type 2 diabetic Goto‐Kakizaki (GK) rats were treated with vehicle or 0.01% (in diet) ipragliflozin with free access to fluid and food. After 8 weeks, GK rats were placed in metabolic cages for 24‐hr. Ipragliflozin decreased body weight, serum glucose and systolic blood pressure, and increased fluid and food intake, urinary glucose and Na+ excretion, urine volume, and renal osmolar clearance, as well as urine vasopressin and solute‐free water reabsorption (TcH2O). BFV, measured by bioimpedance spectroscopy, and fluid balance were similar among the two groups. Urine vasopressin in ipragliflozin‐treated rats was negatively and positively associated with fluid balance and TcH2O, respectively. Ipragliflozin increased the renal membrane protein expression of SGLT2, aquaporin (AQP) 2 phosphorylated at Ser269 and vasopressin V2 receptor. The expression of SGLT1, GLUT2, AQP1, and AQP2 was similar between the groups. In conclusion, the SGLT2 inhibitor ipragliflozin induced a sustained glucosuria, diuresis, and natriuresis, with compensatory increases in fluid intake and vasopressin‐induced TcH2O in proportion to the reduced fluid balance to maintain BFV. These results indicate that the osmotic diuresis induced by SGLT2 inhibition stimulates compensatory fluid intake and renal water reabsorption to maintain BFV.

Measurement of consumed water and daily diuresis proved the pathomorphological manifestations of streptozotocin-induced cystopathy in the experiment on rats according to the results of biochemical studies of blood and urine. It is argued that the desquamation of cells in the transitional epithelium, its atrophy, stratification violation, and baring of the basal membrane are caused by a large volume of urine, which excessively stretches the urinary bladder, destroying the intercellular contacts of the urothelial layer. It is proved that primary hyperglycemia leads to widening of the lumen of the arterioles and moderate thickening of the basal membrane of the micro-hemovessels, and high chronic hyperglycemia – directly triggers the whole cascade of pathomorphological changes: on the 42nd day of the experiment it causes vasoconstriction of the arterioles, and at the later terms – the secondary expansion of the arterioles and venules of the microcirculatory bed of UB (urinary bladder); is the cause of dystrophic changes of endothelial cells, further thickening and lamellar transformation of the basal membrane and plasma permeation of the perivascular connective tissue; causes the appearance of dark involutional myocytes with few organelles and sarcoplasm sequestration. Hydropic dystrophy of smooth myocytes has been found to be associated with the hydration of blood plasma as a result of excessive polydipsia in diabetic animals, and vacuole dystrophy of urothelial cells, enlargement of their size and interstitial edema – with low specific urinary density due to the multiple fast increase of diuresis. It has been established that prolonged high glucosuria and decreased diuresis lead to a decrease in urothelial cell size, compaction of their cytoplasm and ultrastructural readjustment. The increase of the content of glycosylated hemoglobin during the experiment justified the appearance and increase of the sludge-syndrome.

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We have investigated the effect of malaria infection on the urine biochemistry and the renal and hepatic levels of total antioxidant capacity (TAC) in female BWF1 lupus mice. A total of 30 female BWF1 lupus mice were divided into three groups as follows: group (I) control group; group (II) lupus mice infected with live Plasmodium. chabaudi; group (III) lupus mice infected with irradiated P. chabaudi. Mice were killed at day 14 post-infection and plasma samples were collected. live P. chabaudi infection was associated with decreased level of glucose in urine (glucosuria), increased urinary level of both ketones (ketonuria) and blood (hematuria). Additionally, live P. chabaudi infection was associated with increased level of TAC in the renal tissue with decreased level of TAC in the hepatic tissue of infected mice. In conclusion, P. chabaudi infection has a direct effect on the urine biochemistry and the renal and hepatic levels of TAC in BWF1 mice. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the correlation between plasma glucose and HbA1c and the diagnostic accuracy of HbA1c as a screening tool to identify asymptomatic diabetes mellitus in children and adolescents with obesity or asymptomatic glucosuria. A total of 190 subjects who underwent an oral glucose tolerance test (OGTT) to confirm diabetes were categorized into normal glucose tolerance (NGT; n = 117), impaired glucose tolerance (IGT; n = 33), and diabetes (DM; n = 40) according to the OGTT. Forty-seven patients with DM were diagnosed by either OGTT or HbA1c levels. The diagnostic accuracy for the detection of diabetes is based on 47 patients. Laboratory tests were performed after 12 h of fasting. According to the HbA1c criterion, 107 (55.3%) subjects were in the NGT group, 41 (21.6%) were in the IGT group, and 42 (22.1%) were in the DM group. Diagnostic sensitivities of HbA1c and 2-hour plasma glucose level following OGTT (2-h OGTT) for DM were significantly higher than that of fasting plasma glucose, FPG (89.4, 85.1 vs. 63.8%). In addition, the area under the curves of diagnostic criteria was 0.970 for HbA1c, 0.939 for FPG and 0.977 for 2-h OGTT. Mean FPG and 2-h OGTT for HbA1c level >6.5% were 115.2 mg/dL and 181.8 mg/dL, respectively. The optimal HbA1c level cut-off point for predicting DM is 6.15%, with a sensitivity of 95.7% in Korean children and adolescents. The HbA1c criterion ≥6.5% was adequate to detect DM among Korean children and adolescents with obesity or asymptomatic glucosuria. We also recommend HbA1c level of 6.15% as the optimal cut-off point for detecting DM in Korean children and adolescents. [ABSTRACT FROM AUTHOR]

Fanconi- Bickel Syndrome (FBS) is a rare glycogen storage disease (GSD) . Transient diabetes is rarely reported with FBS. We describe a patient with FBS diagnosed by diabetes findings and identification of a mutation in the GLUT2. A male infant, from a consanguineous marriage, presented with hyperglycemia and urinary system infections at 59 days and was given insulin therapy. At age 3 months, insulin was discontinued. Neonatal diabetes may be a first presentation of infants with FBS. [Med-Science 2017; 6(1.000): 111-3]

Background/Aims: Dapagliflozin (DAPA) is a selective inhibitor of the sodium-glucose cotransporter 2 (SGLT2) which induces glucosuria and osmotic diuresis. The therapeutic effect of DAPA in progressing stages of polycystic kidney disease (PKD) has not been studied. Methods: We examined the effect of DAPA in the Han: SPRD rat model of PKD. DAPA (10 mg/kg/day) or vehicle (VEH) was administered orally via gavage to 5 week old male Han: SPRD (Cy/+) or control (+/+) rats (n = 8-9 per group) for 5 weeks. Blood and urine were collected at baseline and after 2.5 and 5 weeks of treatment to assess renal function and albuminuria. At the end of the treatment, rats were sacrificed and kidneys were excised for histological analysis. Results: After 5 weeks of treatment, DAPA-treated Cy/+ and +/+ rats exhibited significantly higher glucosuria, water intake and urine output than VEH-treated rats. DAPA-treated Cy/+ rats also exhibited significantly higher clearances for creatinine and BUN and less albuminuria than VEH-treated Cy/+ rats. DAPA treatment for 5 weeks resulted in a significant increase of the kidney weight in Cy/+ rats but no change in cyst growth. The degree of tubular epithelial cell proliferation, macrophage infiltration and interstitial fibrosis was also similar in DAPA-and VEH-treated Cy/+ rats. Conclusion: The induction of glucosuria with the SGLT2-specific inhibitor DAPA was associated with improved renal function and decreased albuminuria, but had no effect on cyst growth in Cy/+ rats. Overall the beneficial effects of DAPA in this PKD model were weaker than the previously described effects of the combined SGLT1/2 inhibitor phlorizin.

Approximately 20-40% of all diabetic patients experience chronic kidney disease, which is related to higher mortality (cardiovascular and all-cause). A large body of evidence suggests that renal hypoxia is one of the main forces that drives diabetic kidney disease, both in its early and advanced stages. It promotes inflammation, generation of intrarenal collagen, capillary rarefaction and eventually accumulation of extracellular matrix that destroys normal renal architecture. SGLT2 inhibitors are unquestionably a practice-changing drug class and a valuable weapon for patients with type 2 diabetes and chronic kidney disease. They have achieved several beneficial kidney effects after targeting multiple and interrelated signaling pathways, including renal hypoxia, independent of their antihyperglycemic activities. This manuscript discusses the pathophysiological concepts that underly their possible effects on modulating renal hypoxia. It also comprehensively investigates both preclinical and clinical studies that explored the possible role of SGLT2 inhibitors in this setting, so as to achieve long-term renoprotective benefits., Competing Interests: The author declares no conflict of interest., (Copyright: © 2023 Termedia & Banach.)

Background: Dipstick urine tests are used for general health screening in Japan, but how the test results (e.g., glucosuria) relate to mortality is unknown.Methods: Subjects participated in a nationwide screening in 2008 in six districts in Japan. We identified those who might have died using the national database of death certificates from 2008 to 2012 (total registered ~ 6 million) and verified candidates with the regional National Health Insurance Agency and public health nurses. Diabetes mellitus (DM) was defined as HbA1c ≥ 6.5%, fasting blood glucose ≥ 126 mg/dl, or medicated for DM. Hazard ratio (HR) and 95% confidence interval (CI) were calculated by Cox proportional hazard analysis. Glucosuria was defined as dipstick ≥ 1 +.Results: Among 209,060 subjects, we identified 2714 fatalities (median follow-up 3.57 years). Crude mortality rates were 1.2% for those without glucosuria and 3.4% for those with glucosuria. After adjusting for sex, age, body mass index, comorbidity (DM, hypertension, and dyslipidemia), history (stroke, heart disease, and kidney disease), and lifestyle (smoking, drinking, walking, and exercise), the HR (95% CI) for dipstick glucosuria was 1.475 (1.166-1.849, P < 0.001). DM subjects with glucosuria (N = 4655) had a higher HR [1.302 (1.044-1.613, P = 0.020)] than DM subjects without glucosuria (N = 20,245), and non-DM subjects with glucosuria (N = 470) had a higher HR [2.511 (1.539-3.833, P < 0.001)] than non-DM subjects without glucosuria (N = 183,690).Conclusion: Dipstick glucosuria significantly affected mortality in Japanese community-based screening participants. [ABSTRACT FROM AUTHOR]

• Analytical performance specifications (APS) are not widely used for urine test strips. • Reflectance quantitative signals should be compared to quantitative reference methods for urine test strip evaluation. • Reflectance signals outclassed ordinal scales in comparison to reference quantitative methods. • Only optimized reflectance thresholds met the minimum EFLM APS for glucose, proteins and albumin. Urinalysis is essential for diagnosing kidney-related medical conditions. Urine test strip analysis serves as an initial and efficient screening method for reflex testing with accurate quantitative methods. Freshly voided urines (n = 206) were analysed using two urine test strip brands on UC-MAX (Menarini) and cobas u 601 (Roche Diagnostics) instruments. Ordinal scale categories and reflectance signals (if available) were both used for the comparison with reference quantitative methods for glucose, proteins and albumin (cobas 503). Samples were considered positive when glucose > 15 or ≥ 54 mg/dL, proteins ≥ 200 mg/L and albumin ≥ 10 mg/L. Optimized reflectance thresholds were calculated by ROC curve analysis. Analytical performance specifications (APS) for trueness of test strip were gathered from the EFLM guideline (FP D , FN G , FN C). Reflectance signals were significantly lower in urine samples considered positive by the reference method (p < 0.0001). Reflectance signals were also correlated with quantitative measurements, showing strong correlation (0.754 to 0.969). Only the use of optimized reflectance thresholds on cobas u 601 achieved at least the minimum EFLM APS (FP D < 20%, FN G < 50% and FN C < 10%). The use of reflectance signals from urine test strips enhanced accuracy for glucose, proteins, and albumin measurement and may contribute to improve diagnosis of diverse kidney-related conditions. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a complex endocrine and metabolic disorder, and a major public health problem that is rapidly increasing in prevalence. Although a wide range of pharmacotherapies for glycemic control is now available, management of T2DM remains complex and challenging. The kidneys contribute immensely to glucose homeostasis by reabsorbing glucose from the glomerular filtrate. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a new class of antidiabetic agents that inhibit glucose absorption from the kidney independent of insulin, offer a unique opportunity to improve the outcomes of patients with T2DM. In this review, we provide an overview of two globally-approved SGLT2 inhibitors, dapagliflozin and canagliflozin, and discuss their effects and safety. This information will help clinicians to decide whether these drugs will benefit their patients.

Objective: This study aims to describe the overall cumulative effect of sevoflurane on kidney function in healthy patients in terms of mean plasma creatinine, blood urea nitrogen (BUN), creatinine clearance, urinary protein, and glucose excretion at 24 and 72 hours post-anesthesia. Data retrieval: A systematic literature search using MEDLINE and EMBASE as primary search engines was conducted. Articles, relevant abstracts, and citations dated January 1, 1995 to June 30, 2016 were retrieved. Data selection: Search terms included the pharmacological generic name sevoflurane. Search was expanded using the terms "renal function" OR "kidney" function AND "creatinine" OR "blood urea nitrogen" OR "creatinine clearance" OR "proteinuria" OR "glucosuria" OR "nephrotoxicity." Limitations included randomized controlled trial, humans, and ages 19 and above, to include English and non-English text formats. All bibliographic indices for the relevant journals identified were also searched and collated according to relevance. Main outcome measures: Changes in serum/plasma creatinine, BUN, urinary protein, and glucose excretion of sevoflurane at 24 and 72-hours were determined. Results: Six relevant studies were qualified by both the inclusion criteria and inclusion dates. This review consists of 873 patients, 65% are males and 35% are females, with mean age of 56 ± 3 years. Sevoflurane was compared to isoflurane with regard to its nephrotoxic potential. Analyses on the effects of sevoflurane were performed on serum/plasma creatinine, BUN, urinary protein, and glucose excretion at 24 and 72 hours which showed no statistical difference between sevoflurane and isoflurane. Conclusion: In an apparently healthy adult without coexisting renal disorder, sevoflurane does not produce elevations in creatinine and BUN above the established upper limit of the reference range. [ABSTRACT FROM AUTHOR]

Almost 20-40% of all patients suffering from diabetes mellitus experience chronic kidney disease, which is related to higher mortality (cardiovascular and all-cause). The implication of several pathophysiological mechanisms (hemodynamic, tubular, metabolic and inflammatory) in the pathogenesis of diabetic kidney disease generates an urgent need to develop multitarget therapeutic strategies to face its development and progression. SGLT2 inhibitors are undoubtedly a practice-changing drug class for individuals who experience type 2 diabetes and diabetic kidney disease. In vitro studies, exploratory research, sub-analyses of large randomized controlled trials, and investigation of several biomarkers have demonstrated that SGLT2 inhibitors achieved multiple beneficial activities, targeting several renal cellular and molecular pathways independent of their antihyperglycemic activity. These mainly include the reduction in intraglomerular pressure through the restoration of TGF, impacts on the renin-angiotensin-aldosterone system, improvement of renal hypoxia, adaptive metabolic alterations in substrate use/energy expenditure, improvement of mitochondrial dysfunction, and reduction of inflammation, oxidative stress and fibrosis. This manuscript thoroughly investigates the possible mechanisms that underlie their salutary renal effects in patients with diabetes, focusing on several pathways involved and the interplay between them. It also explores their upcoming role in ameliorating the evolution of chronic kidney disease in patients with diabetes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Case Summary: A 3-year-old male neutered Sphynx cat was referred for history of chronically increased liver enzymes and lower urinary tract signs that were first reported when the cat was 5 months old. Urine metabolic profile revealed increased amino aciduria and glucosuria despite normoglycemia, suggesting Fanconi syndrome. Urine sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a banding pattern suggestive of primary tubular damage. Serial blood work showed non-regenerative normocytic normochromic anemia, persistently elevated liver enzymes, worsening azotemia and progressive hyperchloremic metabolic acidosis. Ultrasound revealed irregular kidneys and bilaterally hyperechoic cortices and medullae with a loss of normal corticomedullary distinction. Laparoscopic kidney biopsy revealed a moderate-to-severe chronic interstitial fibrosis with chronic lymphoplasmacytic inflammation, tubular degeneration and atrophy, mild glomerulosclerosis and mild large vascular amyloidosis. Tubular epithelial cell karyomegaly was multifocally evident throughout the kidney. The liver had moderate diffuse zone 1 hepatocellular atrophy, periportal fibrosis, biliary hyperplasia, mild perisinusoidal amyloidosis and hepatocyte karyomegaly in zones 2 and 3. The patient continued to decline and developed polyuria, polydipsia, lethargy and hyporexia irrespective of rigorous management, which failed to curtail the progressive anemia and azotemia. The patient was euthanized 8 months from the onset of clinical signs., Relevance and Novel Information: Fanconi syndrome in cats is a rare condition, with most reports occurring secondary to chlorambucil treatment. This is the first known case of Fanconi syndrome occurring with concurrent hepatorenal epithelial karyomegaly in a young Sphynx cat., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Fanconi syndrome is a disorder of the proximal renal tubule. Recently, advanced genetic analysis technology has revealed that several genes cause familial Fanconi syndrome. We identified a family with autosomal dominant Fanconi syndrome and chronic kidney disease with a novel glycine amidinotransferase (GATM) variant. Case 1 was a 57-year-old Japanese woman. Her father and two siblings had Fanconi syndrome or chronic kidney disease. She presented to our hospital at the age of 34 years with recurrent glucosuria. Her height and weight were 151 cm and 46.6 kg, respectively. Laboratory tests showed glucosuria, hypophosphatemia, hypouricemia, and normal renal function. Her serum creatinine level gradually increased over the following next two decades, and she developed end-stage renal disease. Case 2, the daughter of Case 1, was a 26-year-old woman. Her height and weight were 151 cm and 37.5 kg, respectively. Glucosuria was detected at the age of 13 years, which led to a referral to our hospital. Urinalysis showed low-molecular-weight proteinuria. She was diagnosed with Fanconi syndrome. At the age of 26 years, she had glucosuria, low-molecular-weight proteinuria, hypouricemia, and normal renal function. Genetic testing of both cases revealed a novel missense variant in GATM. The heterozygous missense variants in GATM have been reported to cause familial Fanconi syndrome, which manifests early in life and progresses to renal glomerular failure by mid-adulthood. The novel GATM variant detected in our cases was suspected to be associated with the development of Fanconi syndrome. GATM variants should be tested in patients with idiopathic Fanconi syndrome.

A one year eight month old male child and his nine month old female sibling were presented with Growth retardation, abdominal distension, doll-like faces, hepatomegaly, phosphaturia, proximal renal tubular dysfunction. The elder sibling also presented with glucosuria, hyperglycemia, hypoinsulinemia. The younger one later presented with galactosemia. Biopsy of liver on these two patients revealed the accumulation of glycogen in hepatocytes.

Urinalysis is a widely used diagnostic tool to assist clinicians in determining the etiology of various acute or chronic pathologies. Primary care, general internal medicine, and family medicine clinicians should be adept at identifying indications for urinalyses, in addition to appropriately interpreting their results. In this article, we provide an overview of urinalysis for non-nephrologists., (Copyright © 2023 Elsevier Inc. All rights reserved.)