Glycosuria and Renal Outcomes in Patients with Nondiabetic Advanced Chronic Kidney Disease

Abstract

Sodium glucose cotransporter 2 inhibitors have shown a potential for renoprotection beyond blood glucose lowering. Glycosuria in nondiabetic patients with chronic kidney disease (CKD) is sometimes noted. Whether glycosuria in CKD implies a channelopathy or proximal tubulopathy is not known. The consequence of glycosuria in CKD is also not studied. We performed a cross-sectional study for the association between glycosuria and urine electrolyte excretion in 208 nondiabetic patients. Fractional excretion (FE) of glucose >4% was 3.4%, 6.3% and 62.5% in CKD stage 3, 4 and 5, respectively. These patients with glycosuria had higher FE sodium, FE potassium, FE uric acid, UPCR, and urine NGAL-creatinine ratio. We conducted a longitudinal study for the consequence of glycosuria, defined by dipstick, in 769 nondiabetic patients with stage 4–5 CKD. Glycosuria was associated with a decreased risk for end-stage renal disease (adjusted hazard ratio: 0.77; CI = 0.62–0.97; p = 0.024) and for rapid renal function decline (adjusted odds ratio: 0.63; CI = 0.43–0.95; p = 0.032); but glycosuria was not associated with all-cause mortality or cardiovascular events. The results were consistent in the propensity-score matched cohort. Glycosuria is associated with increased fractional excretion of electrolytes and is related to favorable renal outcomes in nondiabetic patients with stage 5 CKD.

Basal glucosuria in cats

“…In accordance with the results in human patients with non‐diabetic advanced CKD where fractional glucose excretion increases significantly with the decline of renal function (Hung et al, ), all seven cats with IRIS stage 4 (of 4) KD had significantly elevated UGCRs and five of these had a positive glucose dipstick test result. It is unknown, whether hyperglucuria in patients with CKD indicates a proximal tubulopathy, a dysfunction of the SGLTs‐2 or both.…”

“…Increased glucose losses were also observed in a recent study using Wistar rats with alloxan-induced DM. The intraperitoneal application of triiodothyronine at supraphysiological doses resulted in a reduction of kidney sodium-glucose cotransporter 2 (SGLT-2) expression, reduced renal glucose reabsorption and accordingly increased glucosuria(da Silva Teixeira et al, 2016).In accordance with the results in human patients with non-diabetic advanced CKD where fractional glucose excretion increases significantly with the decline of renal function(Hung et al, 2016), all seven cats with IRIS stage 4 (of 4) KD had significantly elevated UGCRs and five of these had a positive glucose dipstick test result. It is unknown, whether hyperglucuria in patients with CKD indicates a proximal tubulopathy, a dysfunction of the SGLTs-2 or both.…”

“…Despite the fact that glucosuria was associated with an increased fractional excretion of electrolytes and a higher urinary protein‐to‐creatinine ratios, glucosuric patients with stage five CKD had a 0.77‐ and 0.63‐fold lower risk for end‐stage renal failure and rapid decline of renal function respectively. The authors speculated that damage of the proximal tubules in this subset of patients might reduce protein reabsorption and hence tubulointerstitial protein accumulation, thereby limiting cytokine activation, inflammation and fibrogenesis (Hung et al, ). Prospective studies are now needed to clarify whether cats with CKD and concomitant pathological glucosuria also have a more favourable outcome.…”

Focal Neurological Seizure due to Hyperglycemic Hyperosmolar Non-Ketotic Syndrome in Undiagnosed Diabetes Mellitus

“…The incidence of neurological dysfunction in HHNS cases currently stands at 10%-25% [ 4 , 5 ]. The mechanism by which neurological dysfunction occurs is yet unclear.…”

“…HHNS occurs due to an elevation of counter-regulatory hormones, including cortisol, glucagon, and catecholamines, which trigger gluconeogenesis, and this results in hyperglycemia and a hyperosmolar state [ 1 ]. When the excess glucose in the blood reaches the kidney and exceeds the transport maximum of the nephron for glucose, the patient experiences osmotic diuresis and profound dehydration [ 4 ]. Presentation of neurological symptoms, such as encephalopathy, hyperkinetic symptoms, or focal or partial seizures, in the setting of significant hyperglycemia (blood glucose greater than 600 mg/dL) should raise suspicion for HHNS, especially if subsequent neurological imaging reveals no abnormality and if the patient improves on continuous insulin infusion and blood glucose control, as did our patient [ 5 , 7 - 9 ].…”