The impact of health-related quality of life (HRQOL) on outcomes remains unclear in chronic kidney disease (CKD) patients despite its importance in socioeconomic aspects and individual health. We aim to identify the relationship between HRQOL and progression of CKD in pre-dialysis patients. A total 1622 patients with CKD were analyzed in the KoreaN cohort Study for Outcomes in patients With Chronic Kidney Disease, a prospective cohort study. CKD progression was defined as one or more of the following: initiation of dialysis or transplantation, a two-fold increase in baseline serum creatinine levels, or a 50% decline in the estimated glomerular filtration rate during the follow-up period. The group with CKD progression had lower scores of HRQOL than the group without CKD progression. A fully adjusted Cox proportional hazard ratio model showed that each low baseline physical and mental component summary score was associated with a higher risk of CKD progression. In Kaplan-Meier survival analysis using propensity score matched data, only low physical component summary scores showed statistical significance with CKD progression. Our study highlights low physical component summary score for an important prognostic factor of CKD progression. Risk-modification interventions for high-risk patients may provide benefits to individuals.
This study aimed to compare the changes in kidney function and the association of tumor size and renal outcomes between patients with renal cell carcinoma (RCC) who underwent radical nephrectomy (RN) and those who underwent partial nephrectomy (PN). A retrospective cohort study was conducted for 557 patients with an RCC of ≤7 cm in diameter and normal contralateral kidney function who underwent PN or RN. PN was performed for 218 (39%) patients. Renal outcomes included the incidence of acute kidney injury (AKI), new-onset chronic kidney disease (CKD), and a ≥25% decline in eGFR 1 year after surgery. Serial changes in eGFR were compared during the 3 years of follow-up. Postoperative eGFR was significantly lower in patients undergoing RN than in those undergoing PN. The incidence of AKI and new-onset CKD was significantly higher in patients after RN (70.1% vs. 24.3%, respectively; P <0.001) than after PN (55.7% vs. 6.2%, respectively; P <0.001). According to the multivariable logistic regression analysis, RN was an independent risk factor for a ≥25% decline in kidney function after 1 year regardless of the tumor size, even after adjusting for various covariates. Compared to PN, RN for even a moderate sized RCC leads to an increased incidence of AKI and new-onset CKD, and is a significant risk factor for kidney function decline. Therefore, PN should be considered as the choice of surgical treatment for RCCs that are ≤7 cm in diameter in order to preserve renal function postoperatively.
In this study based on a large nationally representative sample of Korean adults, we investigated the potential associations of the body mass index (BMI) and waist circumference (WC) with mortality in patients undergoing hemodialysis. We obtained the data of 18,699 participants >20 years of age who were followed up with for 4 years and for whom BMI and WC information were available, using a nationally representative dataset from the Korean National Health Insurance System. Patients were stratified into five levels by their baseline BMI and into six levels by their WC (5-cm increments). A total of 4975 deaths occurred during a median follow-up period of 48.2 months. Participants with a higher BMI had a lower mortality rate than those with a lower BMI. In a fully adjusted Cox regression analysis, being overweight and obese was associated with a significantly lower relative risk of all-cause mortality relative to the reference group. Conversely, the mortality rate was higher among participants with a high WC than among those with a low WC. Participants with the highest WC had a higher risk of mortality, while those with the lowest WC level had a significantly lower risk of mortality. In conclusion, all-cause mortality was positively associated with WC, a measure of abdominal obesity, and inversely associated with BMI, a measure of body volume, in patients undergoing hemodialysis.
Hyperuricemia is a potential risk factor for immunoglobulin A nephropathy (IgAN) progression but its sex-specific effects on IgAN progression remain unclear. This study aimed to determine the effect of serum uric acid on IgAN progression and whether its effect varied according to sex. A total of 4339 patients who diagnosed with IgAN by renal biopsy were retrospectively analyzed. We assessed the association of serum uric acid on IgAN progression using Kaplan–Meier survival analyses and Cox proportional hazards models. The study’s primary end point was IgAN progression that was defined as a 50% decline in the estimated glomerular filtration rate or the initiation of dialysis. On average, the serum uric acid levels were higher in the men than in the women. In the fully adjusted Cox proportional hazards model that considered all subjects, the risk of IgAN progression increased by about 25.6% for every 1 mg/dL increase in the baseline uric acid level. The serum uric acid level was an independent risk factor for IgAN progression in both sexes but its effect was more pronounced in the women (hazard ratio [HR], 1.383; confidence interval [CI],1.263 to 1.514; p < 0.001) than in the men (HR, 1.181; CI, 1.097 to 1.272; p < 0.001) (pinteraction < 0.001). A sensitivity analysis involving serum uric acid quartiles generated consistent and robust results. In conclusion, the serum uric acid level was an independent risk factor for IgAN progression and its effect was more pronounced among the women compared with that among the men.
TGF-β/Smad signaling is a major pathway in progressive fibrotic processes, and further studies on the molecular mechanisms of TGF-β/Smad signaling are still needed for their therapeutic targeting. Recently, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) was shown to improve renal fibrosis, making it an attractive target for chronic kidney diseases (CKDs). Here, we show the mechanism by which PGC-1α regulates the TGF-β/Smad signaling pathway using HK-2 cell lines stably overexpressing empty vector (mock cells) or human PGC1α (PGC1α cells). Stable PGC-1α overexpression negatively regulated the expression of TGF-β-induced epithelial-mesenchymal transition (EMT) markers (fibronectin, E-cadherin, vimentin, and α-SMA) and EMT-related transcription factors (Snail and Slug) compared to mock cells, inhibiting fibrotic progression. Interestingly, among molecules upstream of Smad2/3 activation, the gene expression of only TGFβRI, but not TGFβRII, was downregulated in PGC-1α cells. In addition, the downregulation of TGFβRI by PGC-1α was associated with the upregulation of let-7b/c, miRNA for which the 3′ untranslated region (UTR) of TGFβRI contains a binding site. In conclusion, PGC-1α suppresses TGF-β/Smad signaling activation via targeting TGFβRI downregulation by let-7b/c upregulation.
This study was designed to evaluate the possible renoprotective effects of rosiglitazone (RGT), a peroxisome proliferator-activated subtype γ receptor agonist, in deoxycorticosterone acetate (DOCA)-salt hypertension and its role in endogenous endothelin-1 (ET-1) production and renal fibrosis associated with inflammation. Rats were implanted with DOCA strips (200 mg kg−1) at 1 week after unilateral nephrectomy. DOCA-salt rats received control diet with or without RGT (10 mg kg−1 per day). Systolic blood pressure was measured by the tail-cuff method. Glomerulosclerosis and tubulointerstitial fibrosis were evaluated on kidney sections. The expression of ED-1, cyclooxygenase-2 (COX-2), heat shock protein-25 (HSP25) and transforming growth factor-β1 (TGF-β1) was determined in the kidney by semiquantitative immunoblotting. In DOCA-salt rats, systolic blood pressure was increased, whereas creatinine clearance decreased compared with controls, which were counteracted by RGT treatment. Tubular injury and glomerulosclerois in the histological study were prominent in DOCA-salt rats, which were counteracted by RGT treatment. ET-1 expression was increased in DOCA-salts rats, which was attenuated by RGT treatment. The expression of TGF-β1, ED-1 and COX-2 was increased in DOCA-salt, which was attenuated by RGT treatment. In conclusion, RGT treatment decreases blood pressure and is effective in preventing the progression of renal injury in DOCA-salt hypertension, the mechanisms of which are associated with anti-inflammatory and anti-fibrotic effects through reducing the overexpression of ET-1, ED-1, COX-2 and TGF-β1 in the kidney.