Background: Urinary tract infection (UTI) occurs in 30%-50% of individuals with autosomal dominant polycystic kidney disease (ADPKD). However, the clinical relevance of asymptomatic pyuria in ADPKD patients remains unknown. Methods: We retrospectively reviewed medical records of 256 ADPKD patients who registered to the ADPKD clinic at Seoul National University Hospital from Aug 1999 to Aug 2010. We defined the asymptomatic pyuria as more than 5-9 white blood cells in high-power field with no related symptoms or signs of overt UTI. Patients were categorized into 2 groups depending on its duration and frequency: Group A included non-pyuria and transient pyuria patients; Group B included recurrent and persistent pyuria patients. The association between asymptomatic pyuria and both the development of overt UTI and the deterioration of renal function were examined. Results: With a mean follow-up duration of 65.3 months, 176 (68.8%) out of 256 patients experienced 681 episodes of asymptomatic pyuria and 50 episodes of UTI. The annual incidence of asymptomatic pyuria was 0.492 episodes/patient/year. The patients in group B showed female predominance (58.5% vs. 42.0%, P=0.01) and experienced an upper UTI more frequently (hazard ratio: 4.612, 95% confidence interval: 1.735-12.258; P=0.002, adjusted for gender and hypertension). The annual change in estimated glomerular filtration rate (ΔeGFR) was significantly larger in magnitude in group B than in group A (-2.7±4.56 vs. -1.17±5.8, respectively; P=0.01). Age and Group B found to be the independent variables for ΔeGFR and developing end-stage renal disease (16.0% vs. 4.3%, respectively; P=0.001). Conclusions: Chronic asymptomatic pyuria may increase the risk of developing overt UTI and may contribute to declining renal function in ADPKD.
The long-term prognosis of clinically early IgA nephropathy (IgAN) patients remains to be clarified. We investigated the long-term outcomes of IgAN patients with an apparently benign presentation and evaluated prognostic factors for renal survival. We included patients with biopsy-proven IgAN who had estimated glomerular filtration rates (eGFR) ≥60 mL/min/1.73 m2, normal blood pressure, and proteinuria 1 g/day. The analysis included 153 patients who met the inclusion criteria. At diagnosis, their median systolic blood pressure was 120 (110–130) mmHg, eGFR was 85.9 (74.9–100.1) mL/min/1.73 m2, and proteinuria was 0.25 (0.13–0.38) g/day. Of these, 4 patients died and 6 reached ESRD. The 30-year renal survival rate was 85.5%. Three patients had increased serum creatinine levels and 11 developed proteinuria. Remission was observed in 35 (22.9%) patients. A moderate or severe degree of interstitial fibrosis (adjusted odd ratio [OR] 5.93, 95% confidence interval [CI] 1.44–24.45, P = 0.014) and hypoalbuminemia (adjusted OR 6.18, 95% CI 1.20–31.79, P = 0.029) were independent predictors of the secondary outcome. This study showed that the prognosis of early IgAN was not always favorable, even resulting in progression to ESRD in some cases. Hypoalbuminemia and interstitial fibrosis should also be considered important prognostic factors in clinically early IgAN patients.
1 December 2014 in Clinical Journal of the American Society of Nephrology
Background and objectives The antiproteinuric effect of a renin-angiotensin-aldosterone system blockade can be magnified by dietary salt restriction. This study sought to determine the effect of intensive low-salt diet education on BP and urine albumin excretion in nondiabetic patients with hypertension and albuminuria. Design, setting, participants, & measurements This study was conducted between March of 2012 and March of 2013 as an open-label, randomized, controlled trial. After a run-in period of 8 weeks, all patients received the angiotensin II receptor blocker olmesartan (40 mg daily). Patients were then divided into two groups. One group was treated for another 8 weeks with angiotensin II receptor blocker plus conventional low-salt diet education, and the other group was treated for 8 weeks with angiotensin II receptor blocker plus intensive low-salt diet education. The final analyses was performed with 245 completed patients. Results The amount of daily albuminuria was significantly decreased from 0 (566.0 [25.0–5398.6] mg/d) to 8 weeks (282.5 [16.1–4898.5] mg/d; P<0.001). From 8 to 16 weeks, the 24-hour urinary sodium excretion was decreased by 36.0±5.9 mmol/d in the intensive education group and 8.8±4.9 mmol/d in the conventional education group (interaction P<0.001). Patients who completed intensive low-salt diet education exhibited greater decreases in urinary albumin excretion than the control group (change in albuminuria from 8 to 16 weeks, −154.0 versus 0.4 mg/d; P=0.01). Urinary albumin excretion tended to decrease as the 24-hour urinary sodium excretion amount decreased (R=0.32; 95% confidence interval, 0.20 to 0.43; P<0.001). Conclusions The 24-hour urinary albumin excretion was decreased more in patients in the intensive low-salt diet education group than patients in the conventional education group. Weekly intensive education on a low-salt diet would be a suitable method for clinical practice.
The nature of cost-saving effects of early referral to a nephrologist in patients with chronic kidney disease (CKD) is not fully evaluated. We evaluated the health care costs before and after dialysis according to the referral time. A total of 879 patients who were newly diagnosed as having end-stage renal disease from August 2008 to June 2011 were prospectively enrolled. The early referral (ER) group was defined as patients who were referred to a nephrologist more than a year before dialysis and had visited a nephrology clinic 2 or more times. Patients whose referral time was less than a year were considered the late referral (LR) group. Information about medical costs was acquired from the claim data of the Korea Health Insurance Review and Assessment Service. The total medical costs during the first 12 months after the initiation of dialysis were not different between the 526 ER patients and the 353 LR patients. However, the costs of the ER patients during the first month were significantly lower than those of the LR patients (ER vs. LR: 3029±2219 vs. 3438±2821 US dollars [USD], P = 0.025). The total 12-month health care costs before the initiation of dialysis were significantly lower in the ER group (ER vs. LR: 6206±5873 vs. 8610±7820 USD, P<0.001). In the multivariate analysis, ER significantly lowered the health care costs during the 12 months before (2534.0±436.2 USD, P<0.001) and the first month (428.5±172.3 USD, P = 0.013) after the initiation of dialysis. The ER of patients with CKD to a nephrologist is associated with decreased medical costs during the pretreatment period of renal replacement therapy and the early period of dialysis initiation.
Bilirubin has been reported to protect against kidney injury. However, further studies highlighting the beneficial effects of bilirubin on renal fibrosis and chronic renal function decline are necessary. We assessed a prospective cohort with a reference range of total bilirubin levels. The primary outcome was a 30% reduction in the estimated glomerular filtration rate (eGFR) from baseline, and the secondary outcome was a doubling of the serum creatinine levels, halving of the eGFR and the initiation of dialysis. In addition, experiments with tubular epithelial cells and C57BL/6 mice were performed to investigate the protective effects of bilirubin on kidney fibrosis. As a result, 1,080 patients were included in the study cohort. The study group with relative hyperbilirubinemia (total bilirubin 0.8–1.2 mg/dL) showed a better prognosis in terms of the primary outcome (adjusted hazard ratio (HR) 0.33, 95% confidence interval (CI) 0.19–0.59, P < 0.001) and the secondary outcome (adjusted HR 0.20, 95% CI 0.05 to 0.71, P = 0.01) than that of the control group. Moreover, the bilirubin-treated mice showed less fibrosis in the unilateral ureteral obstruction (UUO) model (P < 0.05). In addition, bilirubin treatment decreased fibronectin expression in tubular epithelial cells in a dose-dependent manner (P < 0.05). Mildly elevated serum bilirubin levels were associated with better renal prognosis, and bilirubin treatment induced a beneficial effect on renal fibrosis. Therefore, bilirubin could be a potential therapeutic target to delay fibrosis-related kidney disease progression.
Background: Periostin is a matricellular protein and plays a vital role in tissue regeneration, fibrosis and wound healing. However, data about its significance in nephrology are limited. We investigated the correlation between urinary periostin excretion and its clinical significance including renal histologic findings and prognosis in IgA nephropathy (IgAN). Methods: Of 399 patients from a glomerulonephritis cohort recruited between January 2009 and December 2014, 314 were enrolled. Serum and urine periostin (uPOSTN) were measured using enzyme-linked immunosorbent assay. We divided the patients into 3 groups by uPOSTN/creatinine (uPOSTN/Cr): group 1 (undetectable), group 2 (lower than the median) and group 3 (higher than the median). Results: The uPOSTN level was correlated with pathologic classifications and both initial and final IDMS-MDRD estimated glomerular filtration rates (eGFRs; p < 0.001). Histologically, group 3 patients were correlated with severe interstitial fibrosis/tubular atrophy (p = 0.004), interstitial inflammation (p = 0.007), hyaline arteriolosclerosis (p = 0.001) and glomerular sclerosis (p < 0.001). A higher initial uPOSTN/Cr level was associated with a greater decline in eGFR during follow-up (p = 0.043 when initial eGFR ≥60; p = 0.025 when eGFR <60 ml/min/1.73 m2), and the renal outcomes with end-stage renal disease (ESRD; p = 0.003), ESRD and/or eGFR decrease of >30% (p = 0.033) and ESRD and/or eGFR decrease of >50% (p = 0.046) occurred significantly more in group 3. In multivariate analysis, uPOSTN group 3 (hazards ratio 2.839, 95% CI 1.013-7.957; p = 0.047) was independently associated with ESRD in IgAN patients. Conclusion: uPOSTN/Cr value at initial diagnosis correlated with renal fibrosis and predicted the renal outcomes in patients with IgAN. It could be a promising urinary biomarker for renal fibrosis.