Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial.

BACKGROUND: Sparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis. METHODS: PROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin-angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850. FINDINGS: Between Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6-110) was -2·7 mL/min per 1·73 m2 per year versus -3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1-week 110) was -2·9 mL/min per 1·73 m2 per year versus -3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI -0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (-42·8%, 95% CI -49·8 to -35·0, with sparsentan versus -4·4%, -15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals. INTERPRETATION: Over 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function. FUNDING: Travere Therapeutics.

Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis.

BACKGROUND: An unmet need exists for focal segmental glomerulosclerosis (FSGS) treatment. In an 8-week, phase 2 trial, sparsentan, a dual endothelin-angiotensin receptor antagonist, reduced proteinuria in patients with FSGS. The efficacy and safety of longer-term treatment with sparsentan for FSGS are unknown. METHODS: In this phase 3 trial, we enrolled patients with FSGS (without known secondary causes) who were 8 to 75 years of age; patients were randomly assigned to receive sparsentan or irbesartan (active control) for 108 weeks. The surrogate efficacy end point assessed at the prespecified interim analysis at 36 weeks was the FSGS partial remission of proteinuria end point (defined as a urinary protein-to-creatinine ratio of ≤1.5 [with protein and creatinine both measured in grams] and a >40% reduction in the ratio from baseline). The primary efficacy end point was the estimated glomerular filtration rate (eGFR) slope at the time of the final analysis. The change in eGFR from baseline to 4 weeks after the end of treatment (week 112) was a secondary end point. Safety was also evaluated. RESULTS: A total of 371 patients underwent randomization: 184 were assigned to receive sparsentan and 187 to receive irbesartan. At 36 weeks, the percentage of patients with partial remission of proteinuria was 42.0% in the sparsentan group and 26.0% in the irbesartan group (P = 0.009), a response that was sustained through 108 weeks. At the time of the final analysis at week 108, there were no significant between-group differences in the eGFR slope; the between-group difference in total slope (day 1 to week 108) was 0.3 ml per minute per 1.73 m2 of body-surface area per year (95% confidence interval [CI], -1.7 to 2.4), and the between-group difference in the slope from week 6 to week 108 (i.e., chronic slope) was 0.9 ml per minute per 1.73 m2 per year (95% CI, -1.3 to 3.0). The mean change in eGFR from baseline to week 112 was -10.4 ml per minute per 1.73 m2 with sparsentan and -12.1 ml per minute per 1.73 m2 with irbesartan (difference, 1.8 ml per minute per 1.73 m2; 95% CI, -1.4 to 4.9). Sparsentan and irbesartan had similar safety profiles, and the frequency of adverse events was similar in the two groups. CONCLUSIONS: Among patients with FSGS, there were no significant between-group differences in eGFR slope at 108 weeks, despite a greater reduction in proteinuria with sparsentan than with irbesartan. (Funded by Travere Therapeutics; DUPLEX ClinicalTrials.gov number, NCT03493685.).

Association between urinary chloride excretion and progression of coronary artery calcification in patients with nondialysis chronic kidney disease: results from the KNOW-CKD study.

BACKGROUND: Urine chloride has recently been suggested as a biomarker of renal tubule function in patients with nondialysis chronic kidney disease (CKD), as low urinary chloride concentration is associated with an increased risk of CKD progression. We investigate the association between urinary chloride excretion and the progression of coronary artery calcification (CAC). METHODS: A total of 1,065 patients with nondialysis CKD were divided into tertiles by spot urine chloride-to-creatinine ratios. The 1st, 2nd, and 3rd tertiles were defined as low, moderate, and high urinary chloride excretion, respectively. The study outcome was CAC progression, which was defined as an increase in coronary artery calcium score of more than 200 Agatston units during the 4-year follow-up period. RESULTS: Compared to moderate urinary chloride excretion, high urinary chloride excretion was associated with decreased risk of CAC progression (adjusted odds ratio, 0.379; 95% confidence interval, 0.190-0.757), whereas low urinary chloride excretion was not associated with risk of CAC progression. Restricted cubic spine depicted an inverted J-shaped curve, with a significant reduction in the risk of CAC progression in subjects with high spot urine chloride-to-creatinine ratios. CONCLUSION: High urinary chloride excretion is associated with decreased risk of CAC progression in patients with nondialysis CKD.

Comparison of dominant and nondominant C3 deposition in primary glomerulonephritis.

BACKGROUND: Alternative complement pathway dysregulation plays a key role in glomerulonephritis (GN) and is associated with C3 deposition. Herein, we examined pathological and clinical differences between cases of primary GN with C3-dominant (C3D-GN) and nondominant (C3ND-GN) deposition. METHODS: We extracted primary GN data from the Korean GlomeruloNEphritis sTudy (KoGNET). C3D-GN was defined as C3 staining two grades greater than C1q, C4, and immunoglobulin via immunofluorescence analysis. To overcome a large difference in the number of patients between the C3D-GN and C3ND-GN groups (31 vs. 9,689), permutation testing was used for analysis. RESULTS: The C3D-GN group exhibited higher serum creatinine (p ≤ 0.001), a greater prevalence of estimated glomerular filtration rate of <60 mL/min/1.72 m2 (p ≤ 0.001), higher (but not significantly so) C-reactive protein level, and lower serum C3 level (p ≤ 0.001). Serum albumin, urine protein/creatinine ratio, number of patients who progressed to end-stage renal disease, and all-cause mortality were comparable between groups. Interstitial fibrosis and mesangial cellularity were greater in the C3D-GN group (p = 0.04 and p = 0.01, respectively) than in the C3ND-GN group. C3 deposition was dominant in the former group (p < 0.001), in parallel with increased subendothelial deposition (p ≤ 0.001). CONCLUSION: Greater progression of renal injury and higher mortality occurred in patients with C3D-GN than with C3ND-GN, along with pathologic differences in interstitial and mesangial changes.

Risk improvement and adverse kidney outcomes in patients with chronic kidney disease: findings from KNOW-CKD.

BACKGROUND: Many trials have attempted to slow the progression of chronic kidney disease (CKD) by modifying specific risk factors, but without achieving satisfactory results. We aimed to evaluate the association between the degree of improvement in multiple risk factors and adverse kidney outcomes. METHODS: This was a prospective observational study of 839 patients with CKD G3-G4. The main predictors were the number of improved risk factors between baseline and year one as follows: a decrease in proteinuria, systolic blood pressure, phosphate, and uric acid, and an increase in hemoglobin and bicarbonate from the baseline status to out of the target range. The primary outcome was a composite one, including CKD progression (50% decline in eGFR or kidney replacement therapy) and all-cause death. RESULTS: Patients whose risk factors eventually improved had more unfavorable baseline profiles of the six considered factors. During 3097.8 person-years of follow-up (median 3.5 years per patient), the composite outcome occurred in 48.0% of patients (incidence rate, 13.0 per 100 person-years). Compared with an improvement of no risk factors, the adjusted HRs (95% CI) for improvement of 1 and ≥ 2 risk factors were 0.96 (0.76-1.22) and 0.53 (0.37-0.75), respectively. The association was not affected by diabetic status or CKD severity. Among the risk factors, proteinuria accounted for the greatest contribution to CKD progression. CONCLUSIONS: In patients with CKD G3-G4, improvement in multiple factors was associated with a decreased risk of CKD progression, suggesting the importance of multifactorial risk management.

Bidirectional association between SBP variability and arterial stiffness in patients with chronic kidney disease: findings from KNOW-CKD study.

OBJECTIVE: Studies on the mutual relationship between blood pressure (BP) variability and arterial stiffness using time-dependent changes in arterial stiffness are scarce. METHODS: In this prospective cohort of Korean patients with chronic kidney disease (CKD) G1-G5 without kidney replacement therapy, we studied the bidirectional association between visit-to-visit SBP variability (VVSV) and arterial stiffness in 1036 participants who underwent brachial-ankle pulse wave velocity (baPWV) measurement at baseline and year four. We constructed multivariable logistic regression models using two analytical sets. First, we determined the VVSV [standard deviation (SD)] of all SBP readings over 4 years, and then calculated the odds ratios (ORs) for arterial stiffness progression according to tertiles of VVSV. Arterial stiffness progression was defined as at least 75th percentile of the difference in baPWV between baseline and year four. Second, we analysed the ORs for at least 75th percentile of the 4-year VVSV according to tertiles of baseline baPWV. RESULTS: Compared with the lowest tertile of VVSV (SD), the ORs [95% confidence interval (95% CI)] for arterial stiffness progression were 1.42 (0.96-2.10) and 1.64 (1.11-2.43) for the middle and highest tertiles, respectively. In the second analysis based on tertiles of baseline baPWV, the ORs for at least 75th percentile of VVSV (SD) were 1.41 (95% CI, 0.95-2.10) and 1.64 (95% CI, 1.04-2.61) for the middle and highest tertiles, respectively. This association was similar in both analytical models when VVSV and baPWV were treated as continuous variables. CONCLUSION: There is a bidirectional relationship between BP variability and arterial stiffness in patients with CKD.

Association of coronary artery calcium with adverse cardiovascular outcomes and death in patients with chronic kidney disease: results from the KNOW-CKD.

BACKGROUND: In East Asian countries, patients with chronic kidney disease (CKD) have lower cardiovascular risk profiles and experience fewer cardiovascular events (CVEs) than those in Western countries. Thus the clinical predictive performance of well-known risk factors warrants further testing in this population. METHODS: The KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) is a multicenter, prospective observational study. We included 1579 participants with CKD G1-G5 without kidney replacement therapy between 2011 and 2016. The main predictor was the coronary artery calcium score (CACS). The primary outcome was a composite of nonfatal CVEs or all-cause mortality. Secondary outcomes included 3-point major adverse cardiovascular events (MACEs; the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke), all CVEs and all-cause mortality. RESULTS: During a median follow-up of 5.1 years, a total of 123 primary outcome events occurred (incidence rate 1.6/100 person-years). In the multivariable Cox model, a 1-standard deviation log increase in the CACS was associated with a 1.67-fold [95% confidence interval (CI), 1.37-2.04] higher risk of the primary outcome. Compared with a CACS of 0, the hazard ratio associated with a CACS >400 was 4.89 (95% CI 2.68-8.93) for the primary outcome. This association was consistent for secondary outcomes. Moreover, inclusion of the CACS led to modest improvements in prediction indices of the primary outcome compared with well-known conventional risk factors. CONCLUSIONS: In Korean patients with CKD, the CACS was independently associated with adverse cardiovascular outcomes and all-cause death. The CACS also showed modest improvements in prediction performance over conventional cardiovascular risk factors.

Comparison of Outcomes of Mild and Severe Community- and Hospital-Acquired Acute Kidney Injury.

PURPOSE: Acute kidney injury (AKI) has shown an increasingly common occurrence among hospitalized patients worldwide. We determined the incidence and compared the short- and long-term outcomes of all stages of community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI), and identified predictors for such outcomes. MATERIALS AND METHODS: This observational, single-center, retrospective study identified patients admitted between January 2013 and December 2013 who developed CA-AKI or HA-AKI. Short- and long-term patient and renal outcomes were analyzed. RESULTS: AKI incidence was 14.3% (1882, CA-AKI 4.8% and HA-AKI 9.5%). The highest 30-day and 1-year mortality were recorded in the CA-AKI group. Thirty-day mortality rate was 11.4% in CA-AKI group and 5.7% in HA-AKI group (p<0.001). One-year mortality rates were 20.1% and 13.3%, respectively (p<0.001). More CA-AKI patients developed kidney failure with replacement therapy within 1 year (27, 4.3% vs. 18, 1.4% respectively, p<0.001). CONCLUSION: In conclusion, patients with CA-AKI had worse short- and long-term outcomes compared to HA-AKI patients. AKI severity and discharge serum creatinine were significant independent predictors of 30-day and 1-year mortality.

The Korean Organ Transplantation Registry (KOTRY): an overview and summary of the kidney-transplant cohort.

BACKGROUND: As the need for a nationwide organ-transplant registry emerged, a prospective registry, the Korean Organ Transplantation Registry (KOTRY), was initiated in 2014. Here, we present baseline characteristics and outcomes of the kidney-transplant cohort for 2014 through 2019. METHODS: The KOTRY consists of five organ-transplant cohorts (kidney, liver, lung, heart, and pancreas). Data and samples were prospectively collected from transplant recipients and donors at baseline and follow-up visits; and epidemiological trends, allograft outcomes, and patient outcomes, such as posttransplant complications, comorbidities, and mortality, were analyzed. RESULTS: From 2014 to 2019, there were a total of 6,129 registered kidney transplants (64.8% with living donors and 35.2% with deceased donors) with a mean recipient age of 49.4 ± 11.5 years, and 59.7% were male. ABO-incompatible transplants totaled 17.4% of all transplants, and 15.0% of transplants were preemptive. The overall 1- and 5-year patient survival rates were 98.4% and 95.8%, respectively, and the 1- and 5-year graft survival rates were 97.1% and 90.5%, respectively. During a mean follow-up of 3.8 years, biopsy-proven acute rejection episodes occurred in 17.0% of cases. The mean age of donors was 47.3 ± 12.9 years, and 52.6% were male. Among living donors, the largest category of donors was spouses, while, among deceased donors, 31.2% were expanded-criteria donors. The mean serum creatinine concentrations of living donors were 0.78 ± 0.62 mg/dL and 1.09 ± 0.24 mg/dL at baseline and 1 year after kidney transplantation, respectively. CONCLUSION: The KOTRY, a systematic Korean transplant cohort, can serve as a valuable epidemiological database of Korean kidney transplants.

Association Between Systolic Blood Pressure Variability and Major Adverse Cardiovascular Events in Korean Patients With Chronic Kidney Disease: Findings From KNOW-CKD.

Background Whether visit-to-visit systolic blood pressure (SBP) variability can predict major adverse cardiovascular events (MACE) in patients with chronic kidney disease is unclear. Methods and Results We investigated the relationship between SDs of visit-to-visit SBP variability during the first year of enrollment and MACE among 1575 participants from KNOW-CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease). Participants were categorized into 3 groups according to tertiles of visit-to-visit SBP variability (SD). The study end point was MACE, defined as a composite of nonfatal myocardial infarction, unstable angina, revascularization, nonfatal stroke, hospitalization for heart failure, or cardiac death. During 6748 patient-years of follow-up (median, 4.2 years), MACE occurred in 64 participants (4.1%). Compared with the lowest tertile of visit-to-visit SBP variability (SD), the hazard ratios (HRs) for the middle and the highest tertile were 1.64 (95% CI, 0.80-3.36) and 2.23 (95% CI, 1.12-4.44), respectively, in a multivariable cause-specific hazard model. In addition, the HR associated with each 5-mm Hg increase in visit-to-visit SBP variability (SD) was 1.21 (95% CI, 1.01-1.45). This association was consistent in sensitivity analyses with 2 additional definitions of SBP variability determined by the coefficient of variation and variation independent of the mean. The corresponding HRs for the middle and highest tertiles were 2.11 (95% CI, 1.03-4.35) and 2.28 (95% CI, 1.12-4.63), respectively, in the analysis with the coefficient of variation and 1.76 (95% CI, 0.87-3.57) and 2.04 (95% CI, 1.03-4.03), respectively, with the variation independent of the mean. Conclusions Higher visit-to-visit SBP variability is associated with an increased risk of MACE in patients with chronic kidney disease. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01630486.

The importance of muscle mass in predicting intradialytic hypotension in patients undergoing maintenance hemodialysis.

BACKGROUND: Patients undergoing hemodialysis are susceptible to sarcopenia. As intracellular reservoirs of water, skeletal muscles are important contributors to intradialytic hypotension. This study was designed to determine the role of skeletal muscle mass in intradialytic hypotension. METHODS: In a cross-sectional study, the body composition of 177 patients was measured immediately after hemodialysis using bioelectrical impedance analysis. The parameters measured were skeletal muscle mass, intracellular and extracellular water contents, total body water, and cell-membrane functionality (in phase angle at 50 kHz). Data from laboratory tests, chest radiography, measurements of handgrip strength and mid-arm circumference, and questionnaires were collected. The main outcome was intradialytic hypotension, defined as more than two episodes of hypotension (systolic blood pressure of <90 mmHg) with intervention over the 3 months following enrollment. Logistic regression models including each parameter related to sarcopenia were compared with a clinical model. RESULTS: Patients with a low ratio of skeletal muscle mass to dry body weight (SMM/WT) had a higher rate of intradialytic hypotension (40.7%). Most low-SMM/WT patients were female, obese, diabetic, and had a lower handgrip strength compared with the other patients. In the high-SMM/WT group, the risk of intradialytic hypotension was lower, with an odds ratio of 0.08 (95% confidence interval [CI], 0.02-0.28) and adjusted odds ratio of 0.06 (95% CI, 0.01-0.29). CONCLUSION: Measurement and maintenance of skeletal muscle can help prevent intradialytic hypotension in frail patients undergoing hemodialysis.

Dominant predictors of early post-transplant outcomes based on the Korean Organ Transplantation Registry (KOTRY).

Data for Asian kidney transplants are very limited. We investigated the relative importance of prognostic markers in Asian kidney transplants by using Korean Organ Transplantation Registry (KOTRY) cohort. Prediction models were developed by data-driven variable selection approach. The relative importance of the selected predictors was measured by dominance analysis. A total of 4854 kidney transplant donor-recipient pairs were analyzed. Overall patient survival rates were 99.8%, 98.8%, and 91.8% at 1, 3, and 5 years, respectively. Death-censored graft survival rates were 98.4%, 97.0%, and 95.8% at 1, 3, and 5 years. Biopsy-proven acute rejection free survival rates were 90.1%, 87.4%, and 87.03% at 1, 3, and 5 years. The top 3 dominant predictors for recipient mortality within 1 year were recipient cardiovascular disease history, deceased donor, and recipient age. The dominant predictors for death-censored graft loss within 1 year were acute rejection, deceased donor, and desensitization. The dominant predictors to acute rejection within 1 year were donor age, HLA mismatched numbers, and desensitization. We presented clinical characteristics of patients enrolled in KOTRY during the last 5 years and investigated dominant predictors for early post-transplant outcomes, which would be useful for clinical decision-making based on quantitative measures.

Insufficient early renal recovery and progression to subsequent chronic kidney disease in living kidney donors.

BACKGROUND/AIMS: Renal recovery of a kidney donor after undergoing nephrectomy though challenging is essential. We aimed to examine the effect of estimated glomerular filtration rate (eGFR) percent change at 1-month post-donation on insufficient kidney function after kidney donation. METHODS: A total of 3,952 living kidney donors who underwent donor nephrectomy from 1982 to 2019 from eight different tertiary hospitals in Korea were initially screened. Percent changes in the eGFR from baseline to 1-month post-donation were calculated. The degree of percent changes was categorized by quartile, and the 1st quartile was regarded as the group with the lowest decreased eGFR at 1-month after donation. The remaining eGFR less than 60 mL/min/1.73 m2 was the end-point. The Cox proportional hazard model was used for evaluating the impact of initial eGFR and eGFR percent change at 1-month post-donation on the condition with remaining eGFR < 60 mL/ min/1.73 m2. In the multivariate analysis, we used variables with a p < 0.1 in the univariate analysis. RESULTS: A total of 1,585 donors were included in the analysis. During 62.2 ± 49.3 months, 13.7% of donors showed renal insufficiency. The 4th (adjusted hazard ratio [aHR], 10.41; 95% confidence interval [CI], 5.15 to 21.04) and the 3rd (aHR, 4.29; 95% CI, 2.15 to 8.56) quartiles of percent change in eGFR and the pre-donation eGFR (aHR, 0.90; 95% CI, 0.88 to 0.92) were associated with the development of renal insufficiency. CONCLUSION: The impact of worse initial renal recovery on renal insufficiency was pronounced in donors with lower pre-donation eGFRs. Additionally, worse initial renal recovery of remaining kidney affected the long-term development of renal insufficiency in kidney donors.

Mayo imaging classification is a good predictor of rapid progress among Korean patients with autosomal dominant polycystic kidney disease: results from the KNOW-CKD study.

BACKGROUND: Mayo imaging classification (MIC) is a useful biomarker to predict disease progression in autosomal dominant polycystic kidney disease (ADPKD). This study was performed to validate MIC in the prediction of renal outcome in a prospective Korean ADPKD cohort and evaluate clinical parameters associated with rapid disease progression. METHODS: A total of 178 ADPKD patients were enrolled and prospectively observed for an average duration of 6.2 ± 1.9 years. Rapid progressor was defined as MIC 1C through 1E while slow progressor was defined as 1A through 1B. Renal composite outcome (doubling of serum creatinine, 50% decline of estimated glomerular filtration rate [eGFR], or initiation of renal replacement therapy) as well as the annual percent change of height-adjusted total kidney volume (mHTKV-α), and eGFR decline (mGFR-α) were compared between groups. RESULTS: A total of 110 patients (61.8%) were classified as rapid progressors. These patients were younger and showed a higher proportion of male patients. Rapid progressor was an independent predictor for renal outcome (hazard ratio, 4.09; 95% confidence interval, 1.23-13.54; p = 0.02). The mGFR-α was greater in rapid progressors (-3.58 mL/min per year in 1C, -3.7 in 1D, and -4.52 in 1E) compared with that in slow progressors (-1.54 in 1A and -2.06 in 1B). The mHTKV-α was faster in rapid progressors (5.3% per year in 1C, 9.4% in 1D, and 11.7% in 1E) compared with that in slow progressors (1.2% in 1A and 3.8% in 1B). CONCLUSION: MIC is a good predictive tool to define rapid progressors in Korean ADPKD patients.

Additive harmful effects of acute kidney injury and acute heart failure on mortality in hospitalized patients.

BACKGROUND: Organ crosstalk between the kidney and the heart has been suggested. Acute kidney injury (AKI) and acute heart failure (AHF) are well-known independent risk factors for mortality in hospitalized patients. This study aimed to investigate if these conditions have an additive effect on mortality in hospitalized patients, as this has not been explored in previous studies. METHODS: We retrospectively reviewed the records of 101,804 hospitalized patients who visited two tertiary hospitals in the Republic of Korea over a period of 5 years. AKI was diagnosed using serum creatinine-based criteria, and AHF was classified using International Classification of Diseases codes within 2 weeks after admission. Patients were divided into four groups according to the two conditions. The primary outcome was all-cause mortality. RESULTS: AKI occurred in 6.8% of all patients (n = 6,920) and AHF in 1.2% (n = 1,244). Three hundred thirty-one patients (0.3%) developed both conditions while AKI alone was present in 6,589 patients (6.5%) and AHF alone in 913 patients (0.9%). Among the 5,181 patients (5.1%) who died, 20.8% died within 1 month. The hazard ratio for 1-month mortality was 29.23 in patients with both conditions, 15.00 for AKI only, and 3.39 for AHF only. The relative excess risk of interaction was 11.85 (95% confidence interval, 2.43-21.27), and was more prominent in patients aged <75 years and those without chronic heart failure. CONCLUSION: AKI and AHF have a detrimental additive effect on short-term mortality in hospitalized patients.

Economic Impact of Donating a Kidney on Living Donors: A Korean Cohort Study.

RATIONALE & OBJECTIVE: Although existing studies have reported adverse health outcomes after kidney donation, its socioeconomic impact on living donors requires further study. STUDY DESIGN: A retrospective observational cohort study including a matched comparison group. SETTING & PARTICIPANTS: 1,285 living kidney donors from 7 tertiary hospitals between 2003 and 2016, and a matched comparison group consisting of the same number of health screening examinees with similar baseline clinical characteristics and socioeconomic status. All participants were receiving Korean national health insurance. EXPOSURE: Kidney donation as reflected in the Korean National Health Insurance System (NHIS) database. OUTCOME: Changes in household economic status estimated by Korean national health insurance fees and changes in employment status reflected in the NHIS database. ANALYTICAL APPROACH: The outcomes of the donor group and matched control group were compared annually using multivariable logistic regression analyses adjusted for clinical and demographic characteristics. RESULTS: The median ages of the donors and matched controls were 45 and 46 years, respectively; 44.6% of both groups were male. Compared to the comparison group, living donors were at higher risk of being unemployed or losing employment during the first 2 years after donation (eg, first-year loss of employment: odds ratio (OR), 2.27 [95% CI, 1.55-3.33]); however, this association did not persist. Donors also had a significantly lower odds of improvement in economic status (OR, 0.57 [95% CI, 0.47-0.71]) and a higher odds of deterioration in financial status (OR, 1.54 [95% CI, 1.23-1.93]) in the first year after transplantation and subsequently. LIMITATIONS: Unmeasured differences between donors and matched controls creating residual selection bias and confounding. CONCLUSIONS: Living kidney donors may suffer loss of employment and poor economic status after their voluntary donation. The socioeconomic impact on these donors should be considered in conjunction with the potential long-term adverse health outcomes after donation.

Association of blood pressure with cardiovascular outcome and mortality: results from the KNOW-CKD study.

BACKGROUND: Optimal blood pressure (BP) control is a major therapeutic strategy to reduce adverse cardiovascular events (CVEs) and mortality in patients with chronic kidney disease (CKD). We studied the association of BP with adverse cardiovascular outcome and all-cause death in patients with CKD. METHODS: Among 2238 participants from the KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD), 2226 patients with baseline BP measurements were enrolled. The main predictor was systolic BP (SBP) categorized by five levels: <110, 110-119, 120-129, 130-139 and ≥140 mmHg. The primary endpoint was a composite outcome of all-cause death or incident CVEs. We primarily used marginal structural models (MSMs) using averaged and the most recent time-updated SBPs. RESULTS: During the follow-up of 10 233.79 person-years (median 4.60 years), the primary composite outcome occurred in 240 (10.8%) participants, with a corresponding incidence rate of 23.5 [95% confidence interval (CI) 20.7-26.6]/1000 patient-years. MSMs with averaged SBP showed a U-shaped relationship with the primary outcome. Compared with time-updated SBP of 110-119 mmHg, hazard ratios (95% CI) for <110, 120-129, 130-139 and ≥140 mmHg were 2.47 (1.48-4.11), 1.29 (0.80-2.08), 2.15 (1.26-3.69) and 2.19 (1.19-4.01), respectively. MSMs with the most recent SBP also showed similar findings. CONCLUSIONS: In Korean patients with CKD, there was a U-shaped association of SBP with the risk of adverse clinical outcomes. Our findings highlight the importance of BP control and suggest a potential hazard of SBP <110 mmHg.

Low-density lipoprotein cholesterol levels and adverse clinical outcomes in chronic kidney disease: Results from the KNOW-CKD.

BACKGROUND AND AIMS: The optimal low-density lipoprotein cholesterol (LDL-C) level to prevent cardiovascular disease in chronic kidney disease (CKD) patients remains unknown. This study aimed to explore the association of LDL-C levels with adverse cardiovascular and kidney outcomes in Korean CKD patients and determine the validity of "the lower, the better" strategy for statin intake. METHODS AND RESULTS: A total of 1886 patients from the KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD) were included. Patients were classified into four LDL-C categories: <70, 70-99, 100-129, and ≥130 mg/dL. The primary outcome was extended major adverse cardiovascular events (eMACEs). Secondary outcomes included all-cause mortality, and CKD progression. During the follow-up period, the primary outcome events occurred in 136 (7.2%) patients (16.9 per 1000 person-years). There was a graded association between LDL-C and the risk of eMACEs. The hazard ratios (95% confidence intervals) for LDL-C categories of 70-99, 100-129, and ≥130 mg/dL were 2.06 (1.14-3.73), 2.79 (1.18-6.58), and 4.10 (1.17-14.3), respectively, compared to LDL-C <70 mg/dL. Time-varying analysis showed consistent findings. The predictive performance of LDL-C for eMACEs was affected by kidney function. Higher LDL-C levels were also associated with significantly higher risks of CKD progression. However, LDL-C level was not associated with all-cause mortality. CONCLUSIONS: This study showed a graded relationship between LDL-C and the risk of adverse cardiovascular outcome in CKD patients. The lowest risk was observed with LDL-C <70 mg/dL, suggesting that a lower LDL-C target may be acceptable.