A Slight Decrease in the Serum Albumin Level Is Associated with the Rapid Progression of Kidney Dysfunction, Even within the Normal Range.

Objective A low-normal albumin level is associated with a high risk of cardiovascular disease and mortality in the general population. However, the relationship between the serum albumin level and the future decline in the kidney function is unclear. We evaluated the effect of the serum albumin level on the decline in the kidney function in the general population. Methods The data used were from 11,000 participants in a voluntary health checkup program conducted between 1998 and 2006 in Japan. The primary outcome for the kidney function was a difference in the estimated glomerular filtration rate (ΔeGFR) of≥3 mL/min/1.73 m2/year. The association of the risk of a decreased kidney function with the albumin level was determined using a logistic regression analysis. We fit separate multivariable logistic regressions for the serum albumin levels (g/dL) as a continuous variable and as categorical data, classified as ≤4.3 (n=2,530), 4.4-4.6 (n=5,427), and≥4.7 (n=3,043). Results Of the 11,000 participants, 346 had a ΔeGFR/year of≥3. Compared with the participants with albumin levels of≥4.7 g/dL, the risk of a decline in the kidney function was higher not only in those with albumin levels of ≤4.3 g/dL [adjusted odds ratio (OR) =2.10, 95% confidence interval (CI): 1.20-2.93] but also in those with levels of 4.4-4.6 g/dL (adjusted OR=1.53, 95% CI: 1.14-2.05). Conclusion A decreased albumin level is an independent risk factor for a rapid decline in the kidney function, even within the normal range.

Clinicopathological Implications of Proteinuria after Long-Term Isolated Hematuria due to Thin Basement Membrane Nephropathy and Focal Segmental Glomerulosclerosis.

A 45-year-old obese man presented with persistent hematuria for 21 years. At the age of 37, he developed hypertension and proteinuria which later increased up to 1.6 g/g creatinine. Kidney biopsy revealed thin basement membrane nephropathy (TBMN) and focal segmental glomerulosclerosis (FSGS), which explained his urinary abnormalities. Although a subgroup of TBMN can be complicated by FSGS, his FSGS was associated with obesity because of its histological features. Reduction of body weight and increasing a dose of angiotensin-receptor blocker could transiently reduce the amount of proteinuria. Clinicopathological implications of proteinuria after long-term hematuria by TBMN and FSGS were further discussed.

Relationship between Xanthine Oxidoreductase Redox and Oxidative Stress among Chronic Kidney Disease Patients.

Xanthine oxidase (XO), an isoform of xanthine oxidoreductase (XOR), is thought to increase the cardiovascular burden among chronic kidney disease (CKD) patients via oxidative radical production. Plasma XOR redox, which is characterized by the ratio of XO to total XOR, changes under different oxidative conditions associated with kidney dysfunction. However, the relationship between plasma XOR redox and oxidative stress (OS) is unclear. Thus, we aimed to clarify whether OS is related to XOR redox. We used the redox state of human serum albumin (HSA) as a marker to investigate the status of OS in CKD patients. HSA is composed of human mercaptoalbumin (HMA), which possesses not oxidized cysteine residues, reversibly oxidized human nonmercaptoalbumin-1 (HNA-1), and strongly oxidized human nonmercaptoalbumin-2 (HNA-2). The subjects included 13 nondialysis patients (7 males and 6 females) with varying degrees of kidney function. We found that ƒ(HMA) was negatively (R = -0.692, P = 0.0071) and ƒ(HNA-1) was positively (R = 0.703, P = 0.0058) correlated with plasma XO/XOR. ƒ(HNA-2) showed no correlation with XO/XOR (R = 0.146, P = 0.6412), indicating that plasma XOR redox is not related to the irreversible oxidation of HSA. In conclusion, plasma XOR redox is closely related to HSA redox, particularly reversible oxidation of HSA.

Uric Acid in the Follow-Up Determines 30% Decline in Estimated GFR Over 2 Years: a Propensity Score Analysis.

BACKGROUND/AIMS: Higher level of serum uric acid (SUA) predicts early entry to dialysis in chronic kidney disease (CKD) patients. However, a short-term effect of SUA remains to be elucidated using a novel surrogate endpoint. METHODS: Japanese CKD stage 3 to 4 patients were retrospectively examined (n= 701). The follow-up level of SUA was estimated as time-averaged uric acid (TA-UA). A propensity score for 6.0, 6.5 or 7.0 mg/dL of TA-UA was respectively calculated using baseline 23 covariates. The time-to-event analysis was performed for 30% decline in estimated GFR over 2 years. RESULTS: Incidence rates over 2 years were 90 of 440 in men and 36 of 261 in women (p = 0.03). Despite the negative result of baseline SUA, stratified Cox regression on the quintiles of the estimated propensity score showed that higher TA-UA of the three thresholds were all significant (crude HR 2.10 to 2.44) even after adjusting for the confounders. Kaplan-Meier analysis after propensity score matching likewise showed worse survival in the patients with the higher TA-UA (HR 3.11 to 4.26). CONCLUSION: Higher SUA increases likelihood of reaching a surrogate endpoint over 2 years. Early intervention for SUA less than 6.0 mg/dL is recommended for slowing CKD progression.