A “C Odyssey”
Qi Chen, Margreet C.M. Vissers in Vitamin C, 2020
Data from the NIH clinical physiology and pharmacokinetic studies showed that ascorbic acid was not excreted in urine at doses less than 100 mg daily in men and 60 mg in women [34,35]. When ascorbic acid was administered intravenously, so that limitations of intestinal absorption were bypassed, all of the administered doses were excreted at the highest doses of 500 and 1250 mg. From these data, it can be inferred that there is a renal threshold for ascorbic acid, and that when plasma and renal tubule ascorbic acid concentrations exceed this threshold, then ascorbic acid will be found in urine. A renal threshold is analogous to that found for phosphate and for glucose. A precise renal threshold has not been published, but it is anticipated that such a threshold can be calculated.
Athletes with Chronic Conditions
Flavia Meyer, Zbigniew Szygula, Boguslaw Wilk in Fluid Balance, Hydration, and Athletic Performance, 2016
As glucose is a very useful substance in the body, it is one that the kidneys will often try to conserve as they filter the blood. When blood glucose is within the normal physiological range, the vast majority of glucose in the filtrate leaving the glomerulus in the kidney is reabsorbed in the proximal tubule (Sherwood et al. 2013). As a result, the amount of glucose found in urine is generally negligible. The average tubular maximum for glucose reabsorption is around 375 mg/min, although a great deal of inter-individual variability exists with respect to this parameter (Johansen et al. 1984). If an individual has an average glomerular filtration rate (GFR), then the renal threshold for glucose is approximately 300 mg/mL. However, not all nephrons have the same tubular maximum, and as such, glucose may be found in the urine before this threshold is reached (Figure 12.1). This generally starts occurring once blood glucose levels reach 9–10 mmol/L (162–180 mg/dL) (Johansen et al. 1984), but can be lower in some individuals and higher in others. The presence of glucose in the urine, known as glucosuria, can lead to substantial water loss through osmotic diuresis (Dhatariya 2008) thereby increasing the risk of dehydration. In individuals with chronic hyper-glycemia (as demonstrated by elevated glycosylated hemoglobin [HbA1c] levels), the risk of dehydration is higher: a renal resistance to vasopressin has been demonstrated in type 1 diabetic individuals with poor blood glucose control (McKenna et al. 2000) which can decrease the kidneys’ ability to conserve water during exercise.
Renal Handling of Glucose, Sodium and Inulin
Lara Wijayasiri, Kate McCombe, Paul Hatton, David Bogod in The Primary FRCA Structured Oral Examination Study Guide 1, 2017
How much glucose is filtered by the kidney, and how much can be reabsorbed?100% of plasma glucose is filtered.Active transport mechanisms become saturated at higher concentrations of solute and their maximum rate of transport (reabsorption) is reached. This is known as the transport maximum (Tm) for a given solute.Glucose reabsorption is proportional to the amount filtered, and hence to its plasma concentration multiplied by the GFR, up to the transport maximum, which is about 180 g/dL or 10 mmol/L of glucose in venous plasma.Once the renal threshold for glucose is reached, not all the filtered glucose is reabsorbed and glucose starts to appear in the urine.
Sotagliflozin and decompensated heart failure: results of the SOLOIST-WHF trial
Published in Expert Review of Clinical Pharmacology, 2021
Syed Raza Shah, Arroj Ali, Sohail Ikram
Sotagliflozin, a sodium–glucose co-transporter 2 (SGLT2) inhibitor, is a novel new diabetic medication introduced for diabetes management. It inhibits sodium-glucose cotransporter-2 (SGLT2) proteins expressed in the proximal convoluted tubule of the kidneys. The SGLT2 transporter is an ideal protein to target for the treatment of diabetes as it is responsible for about 90% of the filtered glucose reabsorption. Typically, the renal threshold for reabsorption of glucose corresponds to a serum glucose concentration of 180 mg/dL. However, in diabetics, the SGLT2 protein becomes upregulated which can worsen hyperglycemia. Inhibiting SGLT2 protein prevents glucose reabsorption in the kidneys, allowing for better glycemic control in diabetic patients. Sotagliflozin is a particularly interesting and unique medication for its dual ability to be a SGLT2 inhibitor, as well as a SGLT1 inhibitor. SGLT1 is the primary glucose transporter of the small intestine. SGLT1 inhibition has been shown to delay postprandial intestinal glucose absorption and can also enhance plasma levels of GLP-1 and GIP. This dual functionality of Sotagliflozin makes it an especially interesting and appealing drug of choice.
Diabetes mellitus and laboratory medicine in sub-Saharan Africa: challenges and perspectives
Published in Acta Clinica Belgica, 2019
Justin C. Cikomola, Antoine S. Kishabongo, Marijn M. Speeckaert, Joris R. Delanghe
The International Diabetes Federation (IDF) proposes the use of glycosuria as a diagnostic test in case of classic diabetes symptoms, where a blood glucose test is not available [4]. For many years, urine glucose testing has been the major method used for diabetes monitoring. Glycosuria tests are associated with a lower sensitivity, ranging from 21–64%. The renal threshold changes from one person to another with a higher threshold in diabetic patients than in the general population. Fluid intake and urine concentration can affect the results. The urine glucose does not reflect the glycemic level at the time of examination and does not give information about hypoglycemic episodes. In addition, some drugs can interfere with the determination of glucose in the urine [27]. Notwithstanding these disadvantages, urine-based tests present some potential benefits that could be useful. These tests are 4–8 times less expensive than single blood glucose tests. They are safe, affordable and feasible for low-income countries with a small health budget and limited human and physical resources. Furthermore, urinalysis has been used for screening of subjects with diabetes risk factors (e.g. subjects with tuberculosis) [28].
An evaluation of canagliflozin for the treatment of type 2 diabetes: an update
Published in Expert Opinion on Pharmacotherapy, 2021
Taichi Minami, Akiko Kameda, Yasuo Terauchi
The pharmacokinetics of canagliflozin was studied in non-diabetic patients with hepatic and renal impairments in the United States. Most of the patients were Caucasian. The patients with hepatic impairment received 300 mg of canagliflozin once daily for 6 consecutive days, and those with renal impairment received 200 mg of canagliflozin in the same period. The mean time to peak plasma concentration (Tmax) was approximately 2 hours, the peak plasma canagliflozin concentration (Cmax) was 3000 ng/ml, and the area under the curve (AUC) was 27,000 ng・h/ml. All the values were similar across the different hepatic function groups. In non-diabetic subjects without kidney impairment (eGFR ≥80 mL/min/1.73), the Tmax was 1.75 hours, Cmax was 1475 ng/ml, and AUC was 14,345 ng・h/ml. Moreover, among the patients with renal impairment (50 mL/min/1.73 ≥ eGFR ≥ 30 mL/min/1.73), the Tmax was similar, whereas the Cmax and AUC increased by 29% and 63%, respectively. The amount of urinary glucose secretion declined as the eGFR decreased; however, the renal threshold for glucose excretion did not change according to kidney function. The urinary glucose secretion increased by 50.7 g/day from baseline in the subjects without kidney impairment and 10.9 g/day in the patients with renal impairment [64].