Glomerular crescents are associated with the risk of type 2 diabetic kidney disease progression: a retrospective cohort study.

BACKGROUND: Diabetic kidney disease (DKD) stands as the predominant cause of chronic kidney disease and end-stage kidney disease. Its diverse range of manifestations complicates the treatment approach for patients. Although kidney biopsy is considered the gold standard for diagnosis, it lacks precision in predicting the progression of kidney dysfunction. Herein, we addressed whether the presence of glomerular crescents is linked to the outcomes in patients with biopsy-confirmed type 2 DKD. METHODS: We performed a retrospective evaluation, involving 327 patients diagnosed with biopsy-confirmed DKD in the context of type 2 diabetes, excluding cases with other glomerular diseases, from nine tertiary hospitals. Hazard ratios (HRs) were calculated using a Cox regression model to assess the risk of kidney disease progression, defined as either ≥ 50% decrease in estimated glomerular filtration rates or the development of end-stage kidney disease, based on the presence of glomerular crescents. RESULTS: Out of the 327 patients selected, ten patients had glomerular crescents observed in their biopsied tissues. Over the follow-up period (median of 19 months, with a maximum of 18 years), the crescent group exhibited a higher risk of kidney disease progression than the no crescent group, with an adjusted HR of 2.82 (1.32-6.06) (P = 0.008). The presence of heavy proteinuria was associated with an increased risk of developing glomerular crescents. CONCLUSION: The presence of glomerular crescents is indeed linked to the progression of type 2 DKD. Therefore, it is important to determine whether there is an additional immune-mediated glomerulonephritis requiring immunomodulation, and it may be prudent to monitor the histology and repeat a biopsy.

Adiponectin-to-leptin ratio and incident chronic kidney disease: Sex and body composition-dependent association.

BACKGROUND: The association between the adiponectin-to-leptin ratio (A/L ratio) and the risk of incident chronic kidney disease (CKD) is poorly understood. This study aimed to investigate the association between A/L ratio and the risk of incident CKD and to examine whether such a relationship varied according to sex and body composition. METHODS: In this prospective community-based cohort, participants with normal kidney function were analysed (N = 5192). The association between the A/L ratio at baseline and the risk of incident CKD, defined as two or more occasions with an estimated glomerular filtration rate of <60 mL/min/m2 or proteinuria of ≥1+ on a dipstick test during the follow-up period, was evaluated using multivariable Cox proportional hazards analyses. Subgroup analyses were conducted based on sex, body mass index (BMI) and the presence of sarcopenia. RESULTS: The participants' mean age was 57.2 ± 8.3 years, and 53.2% were women. The A/L ratio was higher in men compared with women (1.5 [0.8-3.2] and 0.5 [0.3-0.9] µg/ng, P < 0.001). During a median follow-up of 9.8 [9.5-10.0] years, 417 incident CKD events occurred (8.7 per 1000 person-years). Men in the highest quartile of A/L ratio had a lower risk of incident CKD (adjusted hazard ratio [aHR], 0.57; 95% confidence interval [CI], 0.33-0.99) than those in the lowest quartile. Additionally, a 1.0 increase in A/L ratio was associated with a 12% decreased risk of incident CKD in men (aHR, 0.88; 95% CI, 0.80-0.97). However, no significant association was observed in women. In subgroup analysis stratified by BMI and the presence of sarcopenia, the association between a high A/L ratio and a reduced risk of incident CKD was consistent in men with a BMI < 23.0 kg/m2 and those with sarcopenia. However, no significant association was observed between men with a BMI ≥ 23.0 kg/m2 and those without sarcopenia. CONCLUSIONS: A high A/L ratio is an independent marker of a reduced risk of incident CKD in men, especially in those with a BMI < 23.0 kg/m2 and sarcopenia.

Nocturnal systolic blood pressure dipping and progression of chronic kidney disease.

The relationship between declining nocturnal blood pressure (BP) and adverse cardiovascular outcomes is well-recognized. However, the relationship between diurnal BP profile and the risk of chronic kidney disease (CKD) progression is unclear. Herein, we examined the association between nocturnal systolic SBP (SBP) dipping and CKD progression in 1061 participants at the Cardiovascular and Metabolic Disease Etiology Research Center-High Risk (CMERC-HI). The main exposure was diurnal systolic BP (SBP) profile and diurnal SBP difference ([nighttime SBP-daytime SBP] × 100/daytime SBP). The primary outcome was CKD progression, defined as a composite of ≥ a 50% decline in the estimated glomerular filtration rate from baseline or the initiation of kidney replacement therapy. During 4749 person-years of follow-up (median, 4.8 years), the composite outcome occurred in 380 (35.8%) participants. Compared to dippers, the hazard ratios (HRs) for the risk of adverse kidney outcomes were 1.02 (95% confidence interval [CI], 0.64-1.62), 1.30 (95% CI, 1.02-1.66), and 1.40 (95% CI, 1.03-1.90) for extreme dipper, non-dipper, and reverse dipper, respectively. In a continuous modeling, a 10% increase in diurnal SBP difference was associated with a 1.21-fold (95% CI, 1.07-1.37) higher risk of CKD progression. Thus, decreased nocturnal SBP decline was associated with adverse kidney outcomes in patients with CKD. Particularly, patients with non-dipping and reverse dipping patterns were at higher risk for CKD progression than those with a dipping pattern.

Atherogenic indices and risk of chronic kidney disease in metabolic derangements: Gangnam Severance Medical Cohort.

Background: The effects of atherogenic indices on kidney function remain unclear. This study evaluated the association between atherogenic indices and risk of chronic kidney disease (CKD) in adults with metabolic derangements. Methods: A total of 4,176 participants from the Gangnam Severance Medical Cohort (2006-2021), which consisted of participants who had at least one disease related to metabolic derangements including diabetes mellitus, fatty liver, and hypertension were enrolled and atherogenic indices (lipid ratios including atherogenic index of plasma [AIP]) were assessed. The study endpoint was a composite kidney outcome (estimated glomerular filtration rate [eGFR] of <60 mL/min/1.73 m2 in at least two measurements in participants with baseline eGFR of ≥60 mL/min/1.73 m2; ≥30% decrease in eGFR from baseline in participants with baseline eGFR of <60 mL/min/1.73 m2; or the initiation of dialysis or kidney transplantation). Results: During a median follow-up of 6.0 years (interquartile range, 2.5-11.0 years), 1,266 composite kidney outcomes (30.3%) occurred. The highest quartile of AIP showed a higher risk of composite kidney outcome than the lowest quartile (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.12-1.54). This association was consistent when the AIP was treated as a continuous variable (HR per 1.0 increase, 1.51; 95% CI, 1.21-1.88). However, other atherogenic indices did not show significant associations with composite kidney outcome. Adding AIP to the traditional risk model to predict composite kidney outcomes significantly improved the C-index, net reclassification index, and integrated discrimination improvement. The association between high AIP and an increased risk of composite kidney outcome was consistent regardless of subgroup. Conclusion: High AIP was associated with an increased risk of CKD in adults with metabolic derangements.

Machine learning-based 2-year risk prediction tool in immunoglobulin A nephropathy.

Background: This study aimed to develop a machine learning-based 2-year risk prediction model for early identification of patients with rapid progressive immunoglobulin A nephropathy (IgAN). We also assessed the model's performance to predict the long-term kidney-related outcome of patients. Methods: A retrospective cohort of 1,301 patients with biopsy-proven IgAN from two tertiary hospitals was used to derive and externally validate a random forest-based prediction model predicting primary outcome (30% decline in estimated glomerular filtration rate from baseline or end-stage kidney disease requiring renal replacement therapy) and secondary outcome (improvement of proteinuria) within 2 years after kidney biopsy. Results: For the 2-year prediction of primary outcomes, precision, recall, area-under-the-curve, precision-recall-curve, F1, and Brier score were 0.259, 0.875, 0.771, 0.242, 0.400, and 0.309, respectively. The values for the secondary outcome were 0.904, 0.971, 0.694, 0.903, 0.955, and 0.113, respectively. From Shapley Additive exPlanations analysis, the most informative feature identifying both outcomes was baseline proteinuria. When Kaplan-Meier analysis for 10-year kidney outcome risk was performed with three groups by predicting probabilities derived from the 2-year primary outcome prediction model (low, moderate, and high), high (hazard ratio [HR], 13.00; 95% confidence interval [CI], 9.52-17.77) and moderate (HR, 12.90; 95% CI, 9.92-16.76) groups showed higher risks compared with the low group. From the 2-year secondary outcome prediction model, low (HR, 1.66; 95% CI, 1.42-1.95) and moderate (HR, 1.42; 95% CI, 0.99-2.03) groups were at greater risk for 10-year prognosis than the high group. Conclusion: Our machine learning-based 2-year risk prediction models for the progression of IgAN showed reliable performance and effectively predicted long-term kidney outcome.

Short-term blood pressure variability as a potential therapeutic target for kidney disease.

Short-term blood pressure variability (BPV) measured with ambulatory blood pressure (BP) monitoring has been demonstrated to be significant in predicting various clinical outcomes. Short-term BPV is distinguished from long-term BPV based on the time interval in which BP fluctuations are measured. Increased short-term BPV has been linked to detrimental effects on the microvascular structure and contributes to subclinical organ damage in the heart, blood vessels, and kidneys, regardless of the average 24-h BP levels. Short-term BPV can be defined by various measures, including calculated metrics (standard deviation, coefficient of variation, average real variability, weighted standard deviation, variability independent of the mean) or dipping patterns. Nevertheless, the additional role of short-term BPV beyond the predictive value of average 24-h BPs or established risk factors for cardiovascular disease and kidney disease remains unclear. In particular, longitudinal studies that evaluate the association between short-term BPV and kidney function impairment are limited and no conclusive data exist regarding which short-term BPV indicators most accurately reflect the prognosis of kidney disease. The issue of how to treat BPV in clinical practice is another concern that is frequently raised. This paper presents a review of the evidence for the prognostic role of short-term BPV in kidney outcomes. Additionally, this review discusses the remaining concerns about short-term BPV that need to be further investigated as an independent risk modifier.

Association Between Proton Pump Inhibitor Exposure and Acute Kidney Injury After Cardiac Surgery.

OBJECTIVE: To evaluate the association of preoperative proton pump inhibitor (PPI) exposure with incident acute kidney injury (AKI) after cardiac surgery. PATIENTS AND METHODS: The Severance cardiac surgery cohort included 9860 cardiac surgery patients aged 18 years or older. The National Health Insurance Service-senior cohort included 2933 patients aged 60 years or older who underwent cardiac surgery. Preoperative PPI exposure was defined as a PPI prescription within 3 weeks prior to cardiac surgery. Primary outcomes were postoperative AKI and AKI requiring dialysis (AKI-dialysis). RESULTS: In the Severance cardiac surgery cohort after propensity score matching for PPI exposure, incident AKI (44.0% [472 of 1073] vs 40.5% [1304 of 3219]) and AKI-dialysis (5.8% [62 of 1073] vs 3.7% [119 of 3219]) were more common in patients exposed to PPI than in those who were not. Hospital and intensive care unit stay durations were longer among PPI-exposed than PPI-nonexposed patients. Multivariable conditional logistic analyses revealed that PPI exposure was significantly associated with incident AKI (adjusted odds ratio [AOR], 1.21; 95% CI, 1.03 to 1.42; P=.02) and AKI-dialysis (AOR, 1.74; 95% CI, 1.15 to 2.63; P=.009). The National Health Insurance Service-Senior cohort had similar results, revealing a significant association between PPI exposure and incident AKI-dialysis (AOR, 1.87; 95% CI, 1.25 to 2.81; P=.003). Discontinuation of PPI prior to operation was associated with a lower odds of AKI development in both cohorts. CONCLUSION: Preoperative PPI exposure may be a modifiable risk factor for AKI among patients undergoing cardiac surgery.

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.

Short-term Blood Pressure Variability and Incident CKD in Patients With Hypertension: Findings From the Cardiovascular and Metabolic Disease Etiology Research Center-High Risk (CMERC-HI) Study.

RATIONALE & OBJECTIVE: The association between short-term blood pressure variability (BPV) and kidney outcomes is poorly understood. This study evaluated the association between short-term BPV and kidney disease outcomes in people with hypertension. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 1,173 hypertensive participants in the Cardiovascular and Metabolic Disease Etiology Research Center-High Risk (2013-2018) Study with estimated glomerular filtration rate (eGFR) ≥60mL/min/1.73m2. EXPOSURE: Short-term BPV assessed by average real variability (ARV). OUTCOME: Composite kidney disease outcome (30% decline in eGFR from baseline, new occurrence of eGFR <60mL/min/1.73m2, or onset of UACR >300mg/g). ANALYTICAL APPROACH: Multivariable Cox regression analyses to evaluate the association between systolic and diastolic BP ARV (SBP-ARV and DBP-ARV) and outcomes. RESULTS: During a median follow-up of 5.4 [4.1-6.5] years, 271 events of the composite kidney disease outcome occurred (46.5 per 1,000 person-years). Multivariable Cox analysis revealed that the highest SBP-ARV and DBP-ARV tertiles were associated with a higher risk of the composite kidney disease outcome than the lowest tertiles, independent of the 24-hour SBP or DBP levels (HR, 1.64 [95% CI, 1.16-2.33], and 1.60 [95% CI, 1.15-2.24] for SBP-ARV and DBP-ARV, respectively). These associations were consistent when SBP-ARV and DBP-ARV were treated as continuous variables (HR per 1.0-unit greater SBP-ARV, 1.03 [95% CI, 1.01-1.06]; HR per 1.0-unit greater DBP-ARV, 1.04 [95% CI, 1.01-1.08]). These associations were consistent, irrespective of subgroups (age, sex, 24-hour SBP or DBP, and moderate albuminuria). However, other measures of short-term BPV including SD, coefficient of variation, and dipping patterns were not associated with the composite kidney disease outcome. LIMITATIONS: Observational study design, the use of single measurement of 24-hour BP, lack of information on changes in antihypertensive medication during the follow-up. CONCLUSIONS: Short-term BPV is associated with the development of a composite kidney disease outcome in hypertensive patients.

Korean Society of Nephrology 2022 Recommendations on Controversial Issues in Diagnosis and Management of Hyponatremia.

The Korean Society for Electrolyte and Blood Pressure Research, in collaboration with the Korean Society of Nephrology, has published a clinical practice guideline (CPG) document for hyponatremia treatment. The document is based on an extensive evidence-based review of the diagnosis, evaluation, and treatment of hyponatremia with the multidisciplinary participation of representative experts in hyponatremia with methodologist support for guideline development. This CPG consists of 12 recommendations (two for diagnosis, eight for treatment, and two for special situations) based on eight detailed topics and nine key questions. Each recommendation begins with statements graded by the strength of the recommendations and the quality of the evidence. Each statement is followed by rationale supporting the recommendations. The committee issued conditional recommendations in favor of rapid intermittent bolus administration of hypertonic saline in severe hyponatremia, the use of vasopressin receptor antagonists in heart failure with hypervolemic hyponatremia, and syndrome of inappropriate antidiuresis with moderate to severe hyponatremia, the individualization of desmopressin use, and strong recommendation on the administration of isotonic fluids as maintenance fluid therapy in hospitalized pediatric patients. We hope that this CPG will provide useful recommendations in practice, with the aim of providing clinical support for shared decision-making to improve patient outcomes.

Skin Sodium and Blood Pressure Regulation.

Hypertension is a major public health concern due to its high prevalence and increased risk of cardiovascular disease and mortality. Complex traits resulting from both genetic and environmental factors affect the development of hypertension. Among environmental factors, a high salt diet is an important cause for hypertension. Humans show a heterogeneous blood pressure (BP) response to sodium intake. Although the precise mechanisms for the association between salt sensitivity and hypertension have not been fully elucidated, renal sodium handling has been considered to play a pivotal role. However, this conventional view has recently been challenged in that a third compartment, namely, skin may have a role in the regulation of sodium homeostasis. Skin is comprised of a significant portion of interstitium, which is a major extracellular fluid compartment, and its complex capillary network regulates body temperature and skin perfusion. Growing evidence indicates that local regulatory action of cutaneous blood flow as well as salt and water metabolism is associated with systemic BP control. Previous experimental studies have shown that dietary salt loading resulted in nonosmotic sodium accumulation via glycosaminoglycans and lymphatics embedded in the skin that were mediated by several endogenous factors and attenuated an increase in BP. Studies in humans have also suggested that the skin serves as a buffer system for sodium storage and that skin sodium contributes to salt sensitivity and hypertension. Thus, skin sodium storage provides the possibility of being an additional buffering system in response to salt loading and concomitant BP changes in humans.

Urinary Sodium-to-Potassium Ratio and Incident Chronic Kidney Disease: Results From the Korean Genome and Epidemiology Study.

OBJECTIVE: To evaluate the association of sodium-potassium intake balance on kidney function. PATIENTS AND METHODS: Data from the Korean Genome and Epidemiology Study were used. The participants were enrolled between June 1, 2001, and January 31, 2003, and were followed-up until December 31, 2016. The 24-hour excretion levels of sodium and potassium were calculated using the Kawasaki formula with spot urinary potassium and sodium measurements. Participants were categorized into tertiles according to the estimated 24-hour urinary sodium-to-potassium (Na/K) ratio. The primary outcome was incident chronic kidney disease (CKD), defined as an estimated glomerular filtration rate of <60 mL/min per 1.73 m2 in two or more consecutive measurements during the follow-up period. RESULTS: This study included 4088 participants with normal kidney function. The mean age was 52.4±8.9 years, and 1747 (42.7%) were men. The median estimated 24-hour urinary sodium excretion level, potassium excretion level, and Na/K ratio (inter quartile range) were 4.9 (4.1-5.8) g/d, 2.1 (1.8-2.5) g/d, and 2.3 (1.9-2.7) g/d, respectively. During 37,950 person-years of follow-up (median, 11.5 years), 532 participants developed CKD, and the corresponding incidence rate was 14.0 (95% CI, 12.9-15.3) per 1000 person-years. Multivariable Cox hazard analysis revealed that the risk of incident CKD was significantly lower in the lowest tertile than in the highest tertile (HR, 0.78; 95% CI, 0.63-0.97). However, no significant association was found with incident CKD risk when urinary excretion levels of sodium or potassium were evaluated individually. CONCLUSION: A low urinary Na/K ratio may relate with lower CKD development risk in adults with preserved kidney function.

High Triglyceride-Glucose Index with Renal Hyperfiltration and Albuminuria in Young Adults: The Korea National Health and Nutrition Examination Survey (KNHANES V, VI, and VIII).

Background: High triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, is associated with an increased risk of albuminuria in adults. However, the relationship between high TyG index associated with renal hyperfiltration (RHF) and albuminuria among young adults is unclear. Methods: A total of 5420 participants aged 19−39 years were enrolled from the Korean National Health and Nutrition Examination Survey (2011−2014 and 2019) and their TyG index levels were analyzed. RHF was defined as eGFR with residuals > 90th percentile after adjusting for age, sex, weight, and height. Albuminuria was defined as urinary albumin-to-creatinine ratio ≥ 30 mg/g Cr. Logistic regression analyses were used to evaluate the association between TyG index, RHF, and albuminuria. Results: The mean age was 30.7 ± 6.0 years and 46.4% were male. The prevalence of albuminuria and RHF was higher in the higher tertiles of TyG index. In our multivariable model, high TyG index showed higher risk of albuminuria (odds ratio (OR) per 1.0 increase in TyG index, 1.56; 95% confidence interval (CI), 1.24−1.95 and OR in the highest tertile, 1.65; 95% CI, 1.08−2.52). High TyG index was associated with higher risk of RHF (OR per 1.0 increase in TyG index, 1.56; 95% CI, 1.32−1.84 and OR in the highest tertile, 1.73; 95% CI, 1.31−2.30). When participants were divided into with or without RHF, high-TyG index-associated high risk of albuminuria was only observed in those with RHF. Participants with concurrent high TyG index and RHF showed the highest risk of albuminuria. Mediation analysis showed that 54.2% of the relation between TyG index and albuminuria was mediated by RHF (95% CI of indirect effect, 0.27−0.76). Finally, incorporating TyG index into our basic model improved the predictive value for albuminuria only in participants with RHF. Conclusion: High TyG index associated with RHF was the strongest risk factor for albuminuria in this study. Early identification of high TyG index with RHF may prevent future development of CKD in relatively healthy and young adults.

Korean Society of Nephrology 2022 recommendations on controversial issues in diagnosis and management of hyponatremia.

The Korean Society for Electrolyte and Blood Pressure Research, in collaboration with the Korean Society of Nephrology, has published a clinical practice guideline (CPG) document for hyponatremia treatment. The document is based on an extensive evidence-based review of the diagnosis, evaluation, and treatment of hyponatremia with the multidisciplinary participation of representative experts in hyponatremia with methodologist support for guideline development. This CPG consists of 12 recommendations (two for diagnosis, eight for treatment, and two for special situations) based on eight detailed topics and nine key questions. Each recommendation begins with statements graded by the strength of the recommendations and the quality of the evidence. Each statement is followed by rationale supporting the recommendations. The committee issued conditional recommendations in favor of rapid intermittent bolus administration of hypertonic saline in severe hyponatremia, the use of vasopressin receptor antagonists in heart failure with hypervolemic hyponatremia, and syndrome of inappropriate antidiuresis with moderate to severe hyponatremia, the individualization of desmopressin use, and strong recommendation on the administration of isotonic fluids as maintenance fluid therapy in hospitalized pediatric patients. We hope that this CPG will provide useful recommendations in practice, with the aim of providing clinical support for shared decision-making to improve patient outcomes.

Pulse pressure and the risk of renal hyperfiltration in young adults: Results from Korea National Health and Nutrition Examination Survey (2010-2019).

Background: High pulse pressure (PP) is associated with increased risk of decline of kidney function. However, little is known about the association between PP and RHF in young adults. This study aimed to evaluate the association between PP and RHF in healthy young adults. Methods: Data were retrieved from the Korea National Health and Nutrition Examination Survey from 2010 to 2019. A total of 10,365 participants aged 19-39 years with no hypertension and normal kidney function were analyzed. RHF was defined as logarithm transformed estimated glomerular filtration rate (eGFR) with residuals >90th percentile after adjustment for sex, logarithm transformed age, weight, and height. Participants were divided into tertile based on PP levels. Results: The prevalence of RHF was higher in higher PP tertile group (6.6, 10.5, and 12.7% in T1, T2, and T3; P for trend < 0.001). In multivariable logistic regression analyses, the risk for RHF was increased in higher PP tertiles compared to the lowest tertile [odds ratio (OR), 1.42; 95% confidence interval (CI), 1.19-1.69 in T2; OR, 1.44; 95% CI, 1.20-1.73 in T3]. When PP levels were treated as continuous variable, the risk of RHF was increased 2.36 per 1.0 increase of PP (P < 0.001). In subgroup analyses stratified sex, histories of diabetes or dyslipidemia, and isolated systolic hypertension or isolated diastolic hypertension, there were no significant interactions with PP for the risk for RHF, suggesting that high PP was associated with increased risk of RHF regardless of subgroups. However, the subgroup with BMI showed significant interaction with PP for the risk of RHF, indicating that participants with BMI ≥ 25 kg/m2 were at higher risk of RHF with increasing PP levels than those with BMI < 25 kg/m2 (OR, 1.89; 95% CI, 1.25-2.87 in BMI < 25 kg/m2; OR, 3.16; 95% CI, 1.74-5.73 in BMI ≥ 25 kg/m2; P for interaction = 0.01). Conclusion: High PP is associated with an increased risk of RHF in healthy young adults and this association is prominent in obese young adults. The assessment of PP and associated RHF may give benefit to early detect the potential risk of CKD development in young adults.

Korean Society of Nephrology 2022 Recommendations on controversial issues in diagnosis and management of hyponatremia.

The Korean Society for Electrolyte and Blood Pressure Research, in collaboration with the Korean Society of Nephrology, has published a clinical practice guideline (CPG) document for hyponatremia treatment. The document is based on an extensive evidence-based review of the diagnosis, evaluation, and treatment of hyponatremia with the multidisciplinary participation of representative experts in hyponatremia with methodologist support for guideline development. This CPG consists of 12 recommendations (two for diagnosis, eight for treatment, and two for special situations) based on eight detailed topics and nine key questions. Each recommendation begins with statements graded by the strength of the recommendations and the quality of the evidence. Each statement is followed by rationale supporting the recommendations. The committee issued conditional recommendations in favor of rapid intermittent bolus administration of hypertonic saline in severe hyponatremia, the use of vasopressin receptor antagonists in heart failure with hypervolemic hyponatremia, and syndrome of inappropriate antidiuresis with moderate to severe hyponatremia, the individualization of desmopressin use, and strong recommendation on the administration of isotonic fluids as maintenance fluid therapy in hospitalized pediatric patients. We hope that this CPG will provide useful recommendations in practice, with the aim of providing clinical support for shared decision-making to improve patient outcomes.

Clinical significance of hemodialysis quality of care indicators in very elderly patients with end stage kidney disease.

INTRODUCTION: Improvement in life expectancy has increased the number of very elderly patients undergoing hemodialysis. However, it is not clear which quality measures for hemodialysis should be employed in this population. Therefore, in this paper we investigated the association between major adverse cardiovascular and cerebrovascular events (MACCE) indicators of hemodialysis quality in very elderly patients. PATIENTS AND METHODS: Data regarding a total of 29,692 patients undergoing maintenance hemodialysis (median age 61 years, 41.5% females) who participated in a national hemodialysis quality assessment program were analyzed. They were divided into < 80 years and ≥ 80 years age groups. The primary and secondary outcomes were MACCE and all-cause mortality, respectively. The association between the outcomes and some of the most widely used standard hemodialysis quality-of-care indicators, including spKt/V, hemoglobin, serum calcium, serum phosphate, and albumin levels, was evaluated. To explore the association between Cox proportional hazard models were constructed. Model 1 was adjusted for age and sex. Model 2 included additional demographic characteristics, such as Charlson Comorbidity Index (excluding diabetes), diabetes, cause of ESKD, dialysis vintage, BMI, and pre-dialysis systolic blood pressure. Model 3 was further adjusted for the main medications. To evaluate the relationship between MACCE risk and quality assessment indicators as a continuous variable, cubic spline analyses were conducted. RESULTS: During a median follow-up of 3.7 years, MACCE occurred at a higher rate in the ≥ 80-years group than in the < 80-years group (282.0 vs. 110.1 events/1000 person-years). Multivariate Cox regression analysis revealed that spKt/V, serum calcium and phosphate, and hemoglobin levels were associated with MACCE and all-cause mortality risk in patients aged < 80 years. However, these indicators showed no significant relationship with MACCE and all-cause mortality in patients aged ≥ 80 years. Low serum albumin levels were significantly associated with increased MACCE and all-cause mortality risks, regardless of age. CONCLUSION: In conclusion, hemodialysis quality-of-care indicators including spKt/V, serum calcium and phosphate levels, and hemoglobin were not related to MACCE or all-cause mortality in very elderly hemodialysis patients. However, lower serum albumin levels were associated with poor outcomes, regardless of patient age. Assuring nutritional status rather than improving hemodialysis management adequacy may be more beneficial for improving outcomes in very elderly hemodialysis patients. Further prospective evaluations are needed to confirm these findings.

Preoperative Ionized Magnesium Levels and Risk of Acute Kidney Injury After Cardiac Surgery.

RATIONALE & OBJECTIVE: Although postoperative acute kidney injury (AKI) is a serious complication after cardiac surgery, preventive measures are limited. Despite the known association of preoperative low magnesium levels with cardiac surgery-related atrial fibrillation, the association between preoperative magnesium concentration and postoperative AKI has not been fully elucidated. This study evaluated the association between preoperative serum magnesium level and the development of AKI after cardiac surgery. STUDY DESIGN: Retrospective observational cohort study. SETTING & PARTICIPANTS: Patients aged≥18 years who underwent cardiac surgery at 2 South Korean tertiary hospitals between 2006 and 2020 were identified from medical records. Patients with missing information, an estimated glomerular filtration rate<15mL/min/1.73m2, receiving maintenance dialysis, or a history of AKI treated by dialysis within 1 year before surgery were excluded. EXPOSURE: Preoperative serum magnesium levels. OUTCOME: Postoperative AKI within 48 hours after surgery, defined using the Acute Kidney Injury Network (AKIN) criteria, and dialysis-treated AKI within 30 days after surgery. ANALYTICAL APPROACH: Multivariable logistic regression analysis. RESULTS: Among the 9,766 patients (median age, 64.0 years; 60.1% male), postoperative AKI and dialysis-treated AKI were observed in 40.1% and 4.3% patients, respectively. Postoperative AKI was more prevalent in patients with lower serum magnesium levels (44.9%, 41.4%, 39.4%, and 34.8% in quartiles 1-4, respectively). Multivariable logistic regression analysis revealed that the odds ratios (ORs) for postoperative AKI were progressively larger across progressively lower quartiles of serum magnesium concentration (adjusted ORs of 1.53 [95% CI, 1.33-1.76], 1.29 [95% CI, 1.12-1.48], 1.15 [95% CI, 1.01-1.31] for quartiles 1-3, respectively, relative to quartile 4, P for trend<0.001). Preoperative hypomagnesemia (serum magnesium level<1.09mg/dL) was also significantly associated with AKI (adjusted OR, 1.39 [95% CI, 1.10-1.77]) and dialysis-treated AKI (adjusted OR, 1.67 [95% CI, 1.02-2.72]). LIMITATIONS: Causality could not be evaluated in this observational study. CONCLUSIONS: Lower serum magnesium levels were associated with a higher incidence of AKI in patients undergoing cardiac surgery.

Colchicine use and the risk of CKD progression: a multicentre nested case-control study.

OBJECTIVES: Despite the preclinical evidence on protective effects of colchicine against kidney fibrosis, whether colchicine could delay the progression of chronic kidney disease (CKD) in humans remains unknown. This study examined the association between long-term colchicine use and risk of adverse kidney outcome in patients with CKD who were treated for hyperuricaemia or chronic gout. METHODS: We conducted a multicentre, nested, case-control study in three Korean hospitals. Patients were aged ≥19 years; had CKD G3-G4; and used drugs including colchicine, allopurinol and febuxostat for hyperuricaemia or chronic gout during the period from April 2000 to October 2020. Patients with CKD progression, which was defined as ≥40% decrease from the baseline estimated glomerular filtration rate or the onset of kidney failure with replacement therapy, were matched to controls based on follow-up time, age and sex. RESULTS: Overall, 3085 patients with CKD progression were matched to 11 715 control patients. Multivariate conditional logistic regression analysis showed that patients with ≥90 cumulative daily colchicine doses were associated with a lower risk of CKD progression [adjusted odds ratio (AOR), 0.77; 95% CI: 0.61, 0.96] than non-users. In the sensitivity analysis with matched CKD stages, the AOR was 0.77 (95% CI: 0.62, 0.97). This association was more pronounced in patients without diabetes or hypertension, and in patients with CKD G3. CONCLUSION: Colchicine use is associated with a lower risk of adverse kidney outcomes in CKD patients with hyperuricaemia, or chronic gout.

PGC-1α inhibits the NLRP3 inflammasome via preserving mitochondrial viability to protect kidney fibrosis.

The NLRP3 inflammasome is activated by mitochondrial damage and contributes to kidney fibrosis. However, it is unknown whether PGC-1α, a key mitochondrial biogenesis regulator, modulates NLRP3 inflammasome in kidney injury. Primary renal tubular epithelial cells (RTECs) were isolated from C57BL/6 mice. The NLRP3 inflammasome, mitochondrial dynamics and morphology, oxidative stress, and cell injury markers were examined in RTECs treated by TGF-ß1 with or without Ppargc1a plasmid, PGC-1α activator (metformin), and siPGC-1α. In vivo, adenine-fed and unilateral ureteral obstruction (UUO) mice were treated with metformin. In vitro, TGF-ß1 treatment to RTECs suppressed the expressions of PGC-1α and mitochondrial dynamic-related genes. The NLRP3 inflammasome was also activated and the expression of fibrotic and cell injury markers was increased. PGC-1α induction with the plasmid and metformin improved mitochondrial dynamics and morphology and attenuated the NLRP3 inflammasome and cell injury. The opposite changes were observed by siPGC-1α. The oxidative stress levels, which are inducers of the NLRP3 inflammasome, were increased and the expression of TNFAIP3, a negative regulator of NLRP3 inflammasome regulated by PGC-1α, was decreased by TGF-ß1 and siPGC-1α. However, PGC-1α restoration reversed these alterations. In vivo, adenine-fed and UUO mice models showed suppression of PGC-1α and TNFAIP3 and dysregulated mitochondrial dynamics. Moreover, the activation of oxidative stress and NLRP3 inflammasome, and kidney fibrosis were increased in these mice. However, these changes were significantly reversed by metformin. This study demonstrated that kidney injury was ameliorated by PGC-1α-induced inactivation of the NLRP3 inflammasome via modulation of mitochondrial viability and dynamics.