Hemoglobin Glycation Index: A Novel Risk Factor for Incident Chronic Kidney Disease in an Apparently Healthy Population.

CONTEXT: Chronic kidney disease (CKD) is a worldwide health problem. Recent literature has shown an association of hemoglobin glycation index (HGI) and CKD in patients with dysglycemia. OBJECTIVE: The aim of this study was to reveal the impact of HGI as a predictor for incident CKD in the general population. METHODS: CKD was defined as dipstick proteinuria or estimated glomerular rate (eGFR) < 60 mL/min/1.73 m2. Impact of HGI on incident CKD was assessed using the data from CKD-free health examinees (N = 23 467, 4.1% with diabetes) followed for a mean of 5.1 years: Cox proportional hazards model was employed with multivariate adjustment for age, systolic blood pressure, eGFR, fasting plasma glucose, body mass index, log[alanine aminotransferase], log[triglycerides], high-density lipoprotein cholesterol, platelet counts, smoking, and sex. Elevated level of HGI in subjects with CKD was ascertained after propensity score matching of another group of health examinees (N = 2580, 7.6% with diabetes). RESULTS: In the former group, CKD developed in 2540 subjects and HGI was the second most robust predictor for CKD, following low eGFR. With adjustment for the 11 covariates, the hazard ratio of HGI (95% CI) for CKD was 1.293 (1.238 to 1.349) (P < .0001). The population attributable risk of HGI for CKD was 4.2%. In the latter group, among 708 subjects matched 1:1 for 9 covariates, HGI was significantly elevated in subjects with CKD (median [interquartile range] -0.208 [-0.504 to -0.156] vs -0.284 [-0.582 to 0.052], P = .03). CONCLUSION: HGI was a novel risk factor for CKD in the general population.

Development of glomerular hyperfiltration, a multiphasic phenomenon.

The trajectory of glomerular filtration rate (GFR) in relation to glomerular hyperfiltration (GHF) has been unknown. It was evaluated retrospectively in 23,982 GHF-free health examinees who were followed for 2-10 yr (mean: 5.1 yr). GFR was estimated by the serum creatinine concentration, and GHF was defined as age- and sex-specific estimated GFR (eGFR) ≥ 95% of the Japanese general population. The temporal profile of eGFR was plotted in a GHF-centered way, which was fitted to a random coefficient linear mixed model. Of the 23,982 subjects, 797 and 23,185 subjects developed or did not develop GHF, respectively, so that they were termed as the GHF(+) and GHF(-) groups. At baseline, median eGFR was significantly elevated in the GHF(+) group compared with in the GHF(-) group: 94.1 versus 77.3 mL/min/1.73 m2 (P < 0.001). Elevation of basal eGFR lasted for a mean (SD) of 3.3 (1.9) yr in the GHF(+) group; mean eGFR then rose to the GHF range, which was 108.5 mL/min/1.73 m2. The eGFR decline after the peak was steeper in the GHF(+) group than in the GHF(-) group: -0.984 versus -0.497 mL/min/1.73 m2/yr (P < 0.001). Baseline eGFR, but no other variable, well predicted incident GHF, with an area under the receiver operating characteristic curve of 0.87 (95% confidence interval: 0.86-0.88). In conclusion, GHF occurs as a chronic, multiphasic phenomenon: initially with a sustained GFR elevation for years, followed by a GFR surge to the GHF range, which was accompanied by accelerated GFR declining.

Prediabetes defined by the International Expert Committee as a risk for development of glomerular hyperfiltration.

AIMS: To clarify if prediabetes defined by the International Expert Committee (PrediabetesIEC) and/or the American Diabetes Society (PrediabetesADA) is a risk for incident glomerular hyperfiltration (GH). METHODS: 24,524 health examinees without diabetes, chronic kidney disease (CKD), GH and antihypertensive treatment at baseline, and repeated examinations at least twice during a mean of 5.3 years were retrospectively analysed. Diabetes was defined as fasting plasma glucose (FPG) ≥ 7.0 mmol/L and/or HbA1c ≥ 47 mmol/mol, CKD by estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 and/or dipstick-positive proteinuria, and GH by upper 95th eGFR in the Japanese adults. PrediabetesIEC was diagnosed by "HbA1c 42-46 mmol/mol and/or FPG 6.1-6.9 mmol/L", PrediabetesADA by "HbA1c 39-46 mmol/mol and/or FPG 5.6-6.9 mmol/L", PrediabetesADA-IEC for the condition met the ADA but not the IEC prediabetes definition, and the ADA-normal glucose regulation (NGRADA) by both HbA1c and FPG lower than PrediabetesADA. Risk of PrediabetesIEC and PrediabetesADA for incident GH was examined by multivariate Cox proportional hazards model with seven covariates and probability of incident GH was calculated on the basis of it. RESULTS: PrediabetesIEC was a significant risk for incident GH [adjusted HR 1.91, 95% CI 1.32-2.71] but PrediabetesADA was not [adjusted HR 1.22, 95% CI 0.93-1.61]. The mean (SD) probability of incident GH was 2.3 (4.5)%, 1.0 (2.3)% and 1.0 (2.4)% for PrediabetesIEC, PrediabetesADA-IEC and NGRADA, respectively: the former was significantly larger than the latter two which were not significantly different from each other. CONCLUSIONS: PrediabetesIEC was an independent risk for incident GH.

Serum sulfatide abnormality is associated with increased oxidative stress in hemodialysis patients.

Sulfatides are major glycosphingolipids of lipoproteins that influence atherosclerosis and blood coagulation. Our previous cross-sectional study of hemodialysis patients showed that serum sulfatide levels decreased markedly with increasing duration of hemodialysis treatment, which may contribute to the development of cardiovascular disease. However, this past study could not demonstrate the time-dependent change in serum sulfatide levels in each patient, and the underlying mechanism is unknown. To confirm the time-dependent aggravation of serum sulfatide abnormality, 95 stable hemodialysis outpatients were followed up for 3 years. To show the underlying mechanisms, we statistically analyzed correlations between serum sulfatide levels and clinical factors, including an oxidative stress marker, malondialdehyde. Serum sulfatides were quantified by mass spectrometry after conversion to lysosulfatides. Malondialdehyde was measured using a colorimetric assay. The results showed a time-dependent decrease in serum sulfatide levels associated with increased malondialdehyde levels, although the absolute level of serum malondialdehyde does not determine the baseline level of serum sulfatides. Multiple linear regression analysis showed a significant correlation only between the time-dependent change in serum sulfatide levels and the time-dependent change in serum malondialdehyde levels. This study demonstrated, for the first time, a time-dependent aggravation of serum sulfatide abnormality in hemodialysis patients, as well as the potential relationship between serum sulfatide abnormality and increasing oxidative stress. These findings suggest that oxidative stress might be an aggravating factor in serum sulfatide abnormality. As continuation of hemodialysis treatment hardly improves abnormal serum sulfatide levels or increased oxidative stress, development of novel therapeutic strategies may be important.

Hypoglycaemic coma due to adrenal failure in a chronic haemodialysis patient.

A 62-year-old man, receiving chronic haemodialysis and suffering from alcoholic liver cirrhosis and chronic pancreatitis, presented with hypoglycaemic coma. Plasma cortisol was undetectable (< 5.5 nmol/L) with suppressed adrenocorticotropic hormone (ACTH), which established a diagnosis of adrenal failure due to ACTH deficiency. Twenty-five milligrams of oral hydrocortisone eradicated hypoglycaemia. Presentation of adrenal failure in this patient was atypical because he was hypertensive, serum electrolytes including sodium were normal and anaemia was unremarkable, which were all due to end-stage renal disease and its treatment with haemodialysis. As far as we are aware, this is the first case report of hypoglycaemic coma due to adrenal failure in a chronic haemodialysis patient.

[Estimation of glomerular filtration rate by inulin clearance: comparison with creatinine clearance].

Inulin clearance (Cin) is widely believed to be the gold standard of the glomerular filtration rate (GFR). However, in Japan, Cin has not been officially recognized by the Ministry of Health, Labour and Welfare of Japan for clinical use. Creatinine clearance (Ccr) has been used to estimate the renal function of patients, but there have been many studies in which Ccr estimates were GFR falsely high because the metabolism and tubular excretion of creatinine widely varied according to the pathophysiological state of the patient. In the present study, we determined Cin and Ccr simultaneously in 116 adult patients with renal diseases and diabetic mellitus. The clearance study was performed by the modified Wesson's method. The inulin preparation was FFI-1010 (Fuji Yakuhin Co. Ltd.). Inulin in serum and urine was determined by the newly devised enzymatic assay (Toyobo Co. Ltd.), which is specific for inulin. The mean Cin was 35.0 +/- 14.4 ml/min/1.73 m2. The mean Ccr(the enzyme assay) was 63.6 +/- 24.1 ml/min/1.73 m2 and that of the kinetic Jaffe assay was 55.3 +/- 19.3 ml/min/1.73 m2. Mean Ccr/Cin was 1.93 +/- 0.73, 1.69 +/- 0.62, respectively. This ratio was significantly different(p < 0.05) in the degree of reduction of Cin, with values of 2.07 +/- 0.82 (Cin < 40 ml/min/1.73 m2) and 1.64 +/- 0.32(40 < Cin < 80 ml/min/1.73 m2), respectively. Only 8 patients were classified into the same degree of reduced renal function (the Guideline of Japanese Society of Nephrology). The findings of this study suggest that the GFR determined by Ccr could misjudge the renal function of patient and delay the administration of proper treatment of the patient. Introduction of Cin into the clinical field is necessary to avoid this delay.