Executive summary of the Korean Society of Nephrology 2021 clinical practice guideline for optimal hemodialysis treatment.

The Korean Society of Nephrology (KSN) has published a clinical practice guideline (CPG) document for maintenance hemodialysis (HD). The document, 2021 Clinical Practice Guideline on Optimal HD Treatment, is based on an extensive evidence-oriented review of the benefits of preparation, initiation, and maintenance therapy for HD, with the participation of representative experts from the KSN under the methodologists' support for guideline development. It was intended to help clinicians participating in HD treatment make safer and more effective clinical decisions by providing user-friendly guidelines. We hope that this CPG will be meaningful as a recommendation in practice, but not on a regulatory rule basis, as different approaches and treatments may be used by health care providers depending on the individual patient's condition. This CPG consists of eight sections and 15 key questions. Each begins with statements that are graded by the strength of recommendations and quality of the evidence. Each statement is followed by a summary of the evidence supporting the recommendations. There are also a link to full-text documents and lists of the most important reports so that the readers can read further (most of this is available online).

Executive Summary of the Korean Society of Nephrology 2021 Clinical Practice Guideline for Optimal Hemodialysis Treatment.

The Korean Society of Nephrology (KSN) has published a clinical practice guideline (CPG) document for maintenance hemodialysis (HD). The document, 2021 Clinical Practice Guideline on Optimal HD Treatment, is based on an extensive evidence-oriented review of the benefits of preparation, initiation, and maintenance therapy for HD, with the participation of representative experts from the KSN under the methodologists' support for guideline development. It was intended to help clinicians participating in HD treatment make safer and more effective clinical decisions by providing user-friendly guidelines. We hope that this CPG will be meaningful as a recommendation in practice, but not on a regulatory rule basis, as different approaches and treatments may be used by health care providers depending on the individual patient's condition. This CPG consists of eight sections and 15 key questions. Each begins with statements that are graded by the strength of recommendations and quality of the evidence. Each statement is followed by a summary of the evidence supporting the recommendations. There is also a link to full-text documents and lists of the most important reports so that the readers can read further (most of this is available online).

Effect of ambulatory blood pressure monitoring guided antihypertensive treatment on renal progression in patients with chronic kidney disease: a randomized comparative study.

OBJECTIVES: Adequate blood pressure (BP) control is pivotal for managing chronic kidney disease (CKD). The optimal approach for monitoring BP to delay CKD progression is not yet clear. METHODS: Patients with hypertension and CKD stage 3-4 were randomized into ambulatory blood pressure monitoring (ABPM) or office BP groups. All patients had ABPM at baseline and 18 months, and the ABPM group additionally underwent ABPM at 3 and 6 months. Each ABPM result was notified only for the ABPM group. The BP target was daytime ABP less than 135/85 mmHg for the ABPM group and office BP less than 140/90 mmHg for the office BP group. The primary outcome was decrease in estimated glomerular filtration rate (eGFR) during 18 months. RESULTS: A total of 146 patients were randomized into the ABPM (n = 69) and office BP groups (n = 77). Although office BP was comparable in the two groups at baseline, daytime ABP was higher in the ABPM group (median 140 vs. 132 mmHg). Initial eGFR was 35.7 ±â€Š12.5 ml/min per 1.73 m2 in the ABPM group and 34.6 ±â€Š12.0 ml/min per 1.73 m2 in the office BP group. eGFR change was -5.5 [95% confidence interval (95% CI) -7.7 to  -3.4] ml/min per 1.73 m2 in the ABPM group and -5.0 (95% CI -6.9 to -3.0) ml/min per 1.73 m2 in the office BP group (P = 0.704). Renal events occurred in 10 patients (15.6%) from the ABPM group and five (7.1%) from the office BP group (P = 0.120). CONCLUSION: The present study did not show a beneficial effect of ABPM for controlling hypertension in CKD compared with conventional office BP monitoring in terms of renal outcomes.

Urinary Angiotensinogen in addition to Imaging Classification in the Prediction of Renal Outcome in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Intrarenal renin-angiotensin system (RAS) is known to play the major role in the development of hypertension and renal progression in autosomal dominant polycystic kidney disease (ADPKD). Urinary angiotensinogen to creatinine ratio (AGT/Cr) was suggested as a novel biomarker to reflect intrarenal RAS activity. This study was performed to evaluate urinary AGT/Cr as a predictive biomarker for renal function decline in addition to imaging classification in a prospective ADPKD cohort. METHODS: From 2011 to 2016, a total of 364 ADPKD patients were enrolled in the prospective cohort called the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). Among them, a total of 207 subjects in chronic kidney disease stage 1-4 with baseline urinary AGT and total kidney volume and subsequent renal function follow-up data over more than 1 year were included in the analysis. Patients were defined as slow progressors (SP) if they are classified as 1A or 1B by imaging classification whereas rapid progressors (RP) if they are classified as 1C-1E. Patients were divided according to AGT/Cr quartiles and annual estimated glomerular filtration rate (eGFR) slope was compared among highest quartile (hAGT group) and the rest of quartiles (lAGT group). Patients were divided into 4 groups to evaluate the predictive value of urinary AGT/Cr in addition to imaging classification: SP/lAGT, SP/hAGT, RP/lAGT, and RP/hAGT. The Cox regression model was used to evaluate the hazard ratio (HR) between groups. RESULTS: The mean age was 45.9 years and 88.9% had hypertension. Baseline eGFR was 79.0 ± 28.4 mL/min/1.73 m² and median height-adjusted total kidney volume was 788.2 (471.2; 1,205.2) mL/m. The patients in the hAGT group showed lower eGFR (72.4 ± 24.8 vs. 81.1 ± 29.2 mL/min/1.73 m², P = 0.039), lower plasma hemoglobin (13.0 ± 1.4 vs. 13.7 ± 1.6 g/dL, P = 0.007), higher urinary protein to creatinine ratio (0.14 [0.09, 0.38] vs. 0.07 [0.04, 0.12] g/g, P = 0.007) compared to the lAGT group. The hAGT group was an independent risk factor for faster eGFR decline after adjusting for gender, RP, baseline eGFR, and other known risk factors. During median follow-up duration of 4.6 years, a total of 29 renal events (14.0%) occurred. The SP/hAGT group showed significantly higher risk of developing renal outcome compared to SP/lAGT group (HR, 13.4; 95% confidence interval, 1.282-139.324; P = 0.03). CONCLUSION: Urinary AGT/Cr can be a useful predictive marker in the patients with relatively small ADPKD. Various biomarkers should be considered to define RP when implementing novel treatment in the patients with ADPKD.

Author Correction: Genetic Characteristics of Korean Patients with Autosomal Dominant Polycystic Kidney Disease by Targeted Exome Sequencing.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Genetic Characteristics of Korean Patients with Autosomal Dominant Polycystic Kidney Disease by Targeted Exome Sequencing.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the main causes of end-stage renal disease (ESRD). Genetic information is of the utmost importance in understanding pathogenesis of ADPKD. Therefore, this study aimed to demonstrate the genetic characteristics of ADPKD and their effects on renal function in 749 Korean ADPKD subjects from 524 unrelated families. Genetic studies of PKD1/2 were performed using targeted exome sequencing combined with Sanger sequencing in exon 1 of the PKD1 gene and a multiple ligation probe assay. The mutation detection rate was 80.7% (423/524 families, 331 mutations) and 70.7% was novel. PKD1 protein-truncating (PKD1-PT) genotype was associated with younger age at diagnosis, larger kidney volume, lower renal function compared to PKD1 non-truncating and PKD2 genotypes. The PKD1 genotype showed earlier onset of ESRD compared to PKD2 genotype (64.9 vs. 72.9 years old, P < 0.001). In frailty model controlled for age, gender, and familial clustering effect, PKD2 genotype had 0.2 times lower risk for reaching ESRD than PKD1-PT genotype (p = 0.037). In conclusion, our results suggest that genotyping can contribute to selecting rapid progressors for new emerging therapeutic interventions among Koreans.

Bioelectrical impedance analysis as a nutritional assessment tool in Autosomal Dominant Polycystic Kidney Disease.

OBJECTIVE: Autosomal dominant polycystic kidney disease (ADPKD) patients with massive organomegaly suffer from pressure-related complications including malnutrition. In this study, we analyzed the efficacy of segmental bioelectrical impedance analysis (BIA) for objective and quantitative nutritional assessment in ADPKD patients. DESIGN AND METHODS: We conducted a cross-sectional study, to evaluate the clinical utility of segmental BIA for assessing the nutritional status of ADPKD patients. BIA measurements was assessed according to modified subjective global assessment (SGA) scores and were compared with data from a healthy population. The association between BIA measurements and the height adjusted kidney and liver volumes (htTKLV), were analyzed. SUBJECTS: A total of 288 ADPKD patients, aged ≥ 18 years old, were analyzed. MAIN OUTCOME MEASURES: Nutritional status was evaluated with SGA and segmental BIA. The htTKLV were measured in each patients using computed tomonography images. RESULTS: Higher ratios of extracellular water to total body water (ECW/TBW) in the whole-body (ECW/TBWWB), trunk (ECW/TBWTR), and lower extremities (ECW/TBWLE) and lower phase angle of lower extremities (PhALE) correlated with lower SGA scores in the ADPKD population and in both gender. The four parameters, ECW/TBWWB, ECW/TBWTR, and ECW/TBWLE of >0.38 and PhALE of <5.8 θ were associated with malnutrition in ADPKD patients. These correlations were preserved in the subgroup analysis for chronic kidney disease stages 1-3A. Compared to healthy populations' data, body fluid parameters and segmental ECW/TBW values, except for the upper extremities (ECW/TBWUE), were greater in ADPKD patients. Increased htTKLV was an independent risk factor for malnutrition in ADPKD. The highest correlation with htTKLV was observed for the ECW/TBWTR (r = 0.466), followed by ECW/TBWWB (r = 0.407), ECW/TBWLE (r = 0.385), PhALE (r = -0.279), and PhATR (r = 0.215). CONCLUSIONS: These results demonstrated that segmental BIA parameters of ECW/TBWWB, ECW/TBWTR, ECW/TBWLE and PhALE provide useful information on nutritional status including the impact of organomegaly in ADPKD.

Frequent patient retraining at home reduces the risks of peritoneal dialysis-related infections: A randomised study.

The present study, entitled Trial on Education And Clinical outcomes for Home PD patients (TEACH), investigated the effect of frequent retraining at home on the outcomes of peritoneal dialysis (PD). TEACH is a multicentre, open-label, randomised, controlled trial with parallel arms. Patients starting PD were randomized into either the conventional retraining group (CG) or the frequent retraining group (FG). Patients in the FG were given more frequent home visits for retraining. The primary endpoint was exit site infection (ESI). Secondary endpoints were peritonitis, any PD-related infections, hospitalization, technique failure, and patient survival. A generalised estimating equations (GEE) approach was employed for the adjusted effect of training level on the outcomes. Cox regression was employed for peritonitis and other secondary outcomes. The subjects were randomised to either the FG (n = 51) or the CG (n = 53). Although the time of initial training did not differ between the 2 groups, the total time of training was longer and the frequency of training visits was higher in the FG. In the GEE model, the p-values for interactions between groups and time were significant for both ESI and any PD-related infections, suggesting that the event rates of the two groups significantly changed over time. The event rates for the FG decreased over time, and the event rates for the CG increased after month 12. In the older subgroup (age ≥ 60), frequent retraining had a significant effect in the risk reduction of the first episode of peritonitis (adjusted HR 0.01 [0.001-0.35], p = 0.01). Frequent retraining at home reduced the risk of PD-related infections.

Clinical experience with white blood cell-PET/CT in autosomal dominant polycystic kidney disease patients with suspected cyst infection: A prospective case series.

AIMS: Cyst infection (CI) is a common problem in patients with autosomal dominant polycystic kidney disease (ADPKD). Localization is of great importance in CI. We describe the clinical experience with [18F] FDG-labelled white-blood cell (WBC) PET/CT in detecting CI in ADPKD. METHODS: Nineteen ADPKD patients (M:F = 7:12) suspected of having CI were enrolled in this prospective study. All underwent WBC-PET/CT and MRI or CT. The degree of their WBC accumulation was evaluated from the maximal standardized uptake value of cystic wall. RESULTS: Cyst infection was diagnosed in 14 cases [definite (n = 6), probable (n = 1), or possible (n = 7); kidney (n = 11), or liver (n = 3)]. There was no difference in fever or laboratory findings (White blood cell count, C-reactive protein, culture results, and eGFR). The blood culture was positive only in a subset of CI patients (n = 4). Cyst fluid culture yielded bacterial growth in 80% of aspirates. WBC-PET/CT detected 64% of CI cases, whereas conventional imaging, 50%. WBC-PET/CT showed false-positive results in two of five cases with no CI. The reasons for false negatives with WBC-PET/CT were poor host immune reaction, low virulence, or prior antibiotic therapy. Haemorrhagic cysts were the most common cause of false positivity in WBC-PET/CT. However, WBC-PET/CT detected CI in three cases, in which the conventional imaging failed to find CI. CONCLUSIONS: Clinical information may play little role in the diagnosis of CI. WBC-PET/CT can be used to detect CI with better sensitivity in ADPKD patients, circumventing the exposure to contrast media.

Serum hepcidin may be a novel uremic toxin, which might be related to erythropoietin resistance.

The clinical importance of serum hepcidin in non-dialysis chronic kidney disease (CKD) patients is unclear. The database of a large-scale multicentre prospective study in Korea of 2238 patients enrolled from 2011-2016 was analysed. After excluding patients with missing serum hepcidin (n = 125) and haemoglobin (n = 23) levels, the study included 2090 non-dialysis CKD patients. Markers of inflammation and iron status were positively associated with serum hepcidin level, regardless of CKD stage. However, estimated glomerular filtration rate was inversely associated with serum hepcidin level, particularly in patients with CKD stages 3b-5 but not in those with CKD stages 1-3a. Use of erythropoiesis-stimulating agents was associated with increased serum hepcidin levels, particularly in patients with CKD stages 3b-5 but not in those with CKD stages 1-3a, and serum hepcidin levels positively correlated with the dose of erythropoiesis-stimulating agent. These findings suggest that serum hepcidin may be a uremic toxin and play an important role in erythropoietin resistance. However, future prospective studies are needed to confirm our results.

Polycystic Kidney Disease without an Apparent Family History.

The absence of a positive family history (PFH) in 10%-25% of patients poses a diagnostic challenge for autosomal dominant polycystic kidney disease (ADPKD). In the Toronto Genetic Epidemiology Study of Polycystic Kidney Disease, 210 affected probands underwent renal function testing, abdominal imaging, and comprehensive PKD1 and PKD2 mutation screening. From this cohort, we reviewed all patients with and without an apparent family history, examined their parental medical records, and performed renal imaging in all available parents of unknown disease status. Subsequent reclassification of 209 analyzed patients revealed 72.2% (151 of 209) with a PFH, 15.3% (32 of 209) with de novo disease, 10.5% (22 of 209) with an indeterminate family history, and 1.9% (four of 209) with PFH in retrospect. Among the patients with de novo cases, we found two families with germline mosaicism and one family with somatic mosaicism. Additionally, analysis of renal imaging revealed that 16.3% (34 of 209) of patients displayed atypical PKD, most of which followed one of three patterns: asymmetric or focal PKD with PFH and an identified PKD1 or PKD2 mutation (15 of 34), asymmetric and de novo PKD with proven or suspected somatic mosaicism (seven of 34), or focal PKD without any identifiable PKD1 or PKD2 mutation (eight of 34). In conclusion, PKD without an apparent family history may be due to de novo disease, missing parental medical records, germline or somatic mosaicism, or mild disease from hypomorphic PKD1 and PKD2 mutations. Furthermore, mutations of a newly identified gene for ADPKD, GANAB, and somatic mosaicism need to be considered in the mutation-negative patients with focal disease.

Total kidney and liver volume is a major risk factor for malnutrition in ambulatory patients with autosomal dominant polycystic kidney disease.

BACKGROUND: In patients with autosomal dominant polycystic kidney disease (ADPKD), malnutrition may develop as renal function declines and the abdominal organs become enlarged. We investigated the relationship of intra-abdominal mass with nutritional status. METHODS: This cross-sectional study was performed at a tertiary hospital outpatient clinic. Anthropometric and laboratory data including serum creatinine, albumin, and cholesterol were collected, and kidney and liver volumes were measured. Total kidney and liver volume was defined as the sum of the kidney and liver volumes and adjusted by height (htTKLV). Nutritional status was evaluated by using modified subjective global assessment (SGA). RESULTS: In a total of 288 patients (47.9% female), the mean age was 48.3 ± 12.2 years and the mean estimated glomerular filtration rate (eGFR) was 65.3 ± 25.3 mL/min/1.73 m2. Of these patients, 21 (7.3%) were mildly to moderately malnourished (SGA score of 4 and 5) and 63 (21.7%) were at risk of malnutrition (SGA score of 6). Overall, patients with or at risk of malnutrition were older, had a lower body mass index, lower hemoglobin levels, and poorer renal function compared to the well-nourished group. However, statistically significant differences in these parameters were not observed in female patients, except for eGFR. In contrast, a higher htTKLV correlated with a lower SGA score, even in subjects with an eGFR ≥45 mL/min/1.73 m2. Subjects with an htTKLV ≥2340 mL/m showed an 8.7-fold higher risk of malnutrition, after adjusting for age, hemoglobin, and eGFR. CONCLUSIONS: Nutritional risk was detected in 30% of ambulatory ADPKD patients with relatively good renal function. Intra-abdominal organomegaly was related to nutritional status independently from renal function deterioration.

Serum adiponectin and protein-energy wasting in predialysis chronic kidney disease.

OBJECTIVE: Adiponectin (ADPN) has antiatherogenic, anti-inflammatory, and insulin-sensitizing effects. Serum ADPN levels are increased in patients with chronic kidney diseases (CKD), and higher ADPN is paradoxically a predictor of mortality in these patients. The aim of this study was to determine the association between serum ADPN levels and protein-energy wasting (PEW) in predialysis CKD. METHOD: We examined serum ADPN concentrations and PEW in 1303 patients from the KNOW-CKD (KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease) study. PEW was defined as the presence of three or more of the following four indicators: serum albumin <3.8 g/dL, body mass index <23 kg/m2, urine creatinine excretion (UCE) below the lower quartile, and daily dietary protein intake <0.6 g/kg. We analyzed the association between PEW and ADPN using a multivariate regression model after adjustment for socioeconomic factors, comorbidities, and laboratory findings. RESULTS: Among 1303 predialysis CKD patients, 72 (5.5%) had PEW. In multivariate logistic regression analysis, higher ADPN level was associated with PEW (odds ratio, 1.04; 95% confidence interval [CI], 1.01-1.08 by 1 µg/mL ADPN). The highest ADPN quartile was associated with PEW in comparison with the lowest quartile (odds ratio, 10.54; 95% CI, 1.28-86.74). In multiple linear regression with PEW indicators, ADPN was more strongly associated with UCE (ß = -2.21; 95% CI, -4.13 to -0.28; R2 = 0.67). CONCLUSION: High ADPN is independently associated with PEW. Among PEW indicators, serum ADPN is closely associated with UCE as an indirect measure of muscle mass.

Normal body mass index with central obesity has increased risk of coronary artery calcification in Korean patients with chronic kidney disease.

In chronic kidney disease (CKD), overweight and mild obesity have shown the lowest cardiovascular (CV) risk. However, central obesity has been directly associated with CV risk in these patients. This bidirectional relationship of body mass index (BMI) and central obesity prompted us to evaluate CV risk based on a combination of BMI and waist-to-hip ratio (WHR) in nondialysis CKD patients. We included 1078 patients with CKD stage 2 through 5 (nondialysis) enrolled in a nationwide prospective cohort of Korea. Patients were divided into 3 groups by BMI (normal BMI, 18.5-22.9; overweight, 23.0-27.4; and obese, 27.5 and over kg/m2) and were dichotomized by a sex-specific median WHR (0.92 in males and 0.88 in females). Coronary artery calcification (CAC) was determined by multislice computed tomography. CAC (score above 10 Agatston units) was found in 477 patients. Multivariate logistic regression analysis indicated that BMI was not independently associated with CAC. However, WHR showed an independent linear and significant association with CAC (odds ratio, 1.036; 95% confidence interval, 1.007-1.065 per 0.01 increase). Furthermore, when patients were categorized into 6 groups according to a combination of BMI and WHR, normal BMI but higher WHR had the highest risk of CAC compared with the normal BMI with lower WHR group (2.104; 1.074-4.121). Thus, a normal BMI with central obesity was associated with the highest risk of CAC, suggesting that considering BMI and WHR, 2 surrogates of obesity, can help to discriminate CV risk in Korean nondialysis CKD patients.

Clinical Trials and a View Toward the Future of ADPKD.

In light of the advances in the understanding of cystogenesis in clinical syndromes, potential therapeutic targets have been proposed. Among ciliopathies, autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary disease, and is characterized by the progressive enlargement of bilateral renal cysts, resulting in end-stage kidney failure. Progress in genetics and molecular pathobiology has enabled the development of therapeutic agents that can modulate aberrant molecular pathways. Recently, clinical trials using somatostatin analogs and vasopressin receptor antagonists were conducted, and resulted in the approval of tolvaptan in managing kidney disease in some countries. We will summarize the developments of therapeutic agents based on pathogenesis, and discuss recent findings in clinical trials. Moreover, issues such as the timing of the intervention and outcome assessment will be discussed.

Diagnostic performance of 18F-FDG-labeled white blood cell PET/CT for cyst infection in patients with autosomal dominant polycystic kidney disease: a prospective study.

OBJECTIVES: Cyst infection (CI) is a common problem in patients with autosomal dominant polycystic kidney disease (ADPKD) and the accurate detection of infected cysts is very important. We evaluated the diagnostic performance of fluorine-18 fluorodeoxyglucose-labeled white blood cell (WBC) PET/computed tomography (CT) for detection of infected cysts in patients with ADPKD. PATIENTS AND METHODS: Seventeen patients with ADPKD (male : female, 6 : 11; age, 53±9 years) and suspected CI were enrolled in this prospective study. Patients were classified as having definite/probable/possible CI. All patients underwent WBC PET/CT within 2 days of starting antibiotic treatment. The degree of WBC accumulation was evaluated qualitatively by nuclear medicine physicians. The diagnostic performance of WBC PET/CT was evaluated by sensitivity, specificity, positive predictive values, and negative predictive values. These values were compared with those generated from CT scans and MRI. RESULTS: Seven patients were classified as having renal CI (definite 6, probable 1). In this group, WBC PET/CT showed six positive findings and one equivocal finding. Seven patients were diagnosed with possible infection. In this group, WBC PET/CT showed six negative findings and one indeterminate finding. The diagnostic performance of WBC PET/CT showed advantages over CT or MRI scans (sensitivity 85.7%, specificity 87.5%, positive predictive value 85.7%, negative predictive value 87.5%). CONCLUSION: This prospective study shows that WBC PET/CT can provide an accurate diagnosis of CI in patients with ADPKD.

Association of serum adiponectin level with albuminuria in chronic kidney disease patients.

BACKGROUND: Adiponectin, a peptide hormone secreted from adipocytes, exerts anti-diabetic, anti-atherogenic, and anti-inflammatory properties. We aimed to determine the relationship between serum adiponectin levels and albuminuria, and evaluate determinant factors for serum adiponectin in patients with chronic kidney disease (CKD). METHODS: In total, 1442 CKD patients were included and divided into three groups according to their albumin-to-creatinine ratios: patients with normoalbuminuria (N = 228), microalbuminuria (N = 444), and macroalbuminuria (N = 761). Serum adiponectin was specifically assayed with a commercially available enzyme-linked immunosorbent assay kit. RESULTS: Serum adiponectin was significantly higher in patients with macroalbuminuria than in those without macroalbuminuria (9.7 ± 6.0, 12.4 ± 9.0, and 14.9 ± 11.0 µg/mL in patients with normoalbuminuria, microalbuminuria, and macroalbuminuria, respectively). Univariate linear regression analysis showed that the serum adiponectin concentrations were correlated with age, the albumin-to-creatinine ratio, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol, whereas they were negatively correlated with body mass index, the estimated glomerular filtration rate, and serum albumin and triglyceride levels. The stepwise regression multiple analysis showed that sex; the estimated glomerular filtration rate; body mass index; total cholesterol, high-density lipoprotein cholesterol, and triglyceride levels; and logarithm of the albumin-to-creatinine ratio were independently associated with the logarithm of serum adiponectin levels (r = 0.55, p < 0.001). CONCLUSION: Serum adiponectin concentrations are higher in patients with increasing albuminuria, and these levels are associated with renal insufficiency and lipid profiles.

Refining Genotype-Phenotype Correlation in Autosomal Dominant Polycystic Kidney Disease.

Renal disease variability in autosomal dominant polycystic kidney disease (ADPKD) is strongly influenced by the gene locus (PKD1 versus PKD2). Recent studies identified nontruncating PKD1 mutations in approximately 30% of patients who underwent comprehensive mutation screening, but the clinical significance of these mutations is not well defined. We examined the genotype-renal function correlation in a prospective cohort of 220 unrelated ADPKD families ascertained through probands with serum creatinine ≤1.4 mg/dl at recruitment. We screened these families for PKD1 and PKD2 mutations and reviewed the clinical outcomes of the probands and affected family members. Height-adjusted total kidney volume (htTKV) was obtained in 161 affected subjects. Multivariate Cox proportional hazard modeling for renal and patient survival was performed in 707 affected probands and family members. Overall, we identified pathogenic mutations in 84.5% of our families, in which the prevalence of PKD1 truncating, PKD1 in-frame insertion/deletion, PKD1 nontruncating, and PKD2 mutations was 38.3%, 4.3%, 27.1%, and 30.3%, respectively. Compared with patients with PKD1 truncating mutations, patients with PKD1 in-frame insertion/deletion, PKD1 nontruncating, or PKD2 mutations have smaller htTKV and reduced risks (hazard ratio [95% confidence interval]) of ESRD (0.35 [0.14 to 0.91], 0.10 [0.05 to 0.18], and 0.03 [0.01 to 0.05], respectively) and death (0.31 [0.11 to 0.87], 0.20 [0.11 to 0.38], and 0.18 [0.11 to 0.31], respectively). Refined genotype-renal disease correlation coupled with targeted next generation sequencing of PKD1 and PKD2 may provide useful clinical prognostication for ADPKD.

HL156A, a novel AMP-activated protein kinase activator, is protective against peritoneal fibrosis in an in vivo and in vitro model of peritoneal fibrosis.

HL156A is a novel AMP-activated protein kinase (AMPK) activator. We aimed to investigate the protective mechanism of HL156A against peritoneal fibrosis (PF) in in vivo and in vitro models. The rat PF model was induced by daily intraperitoneally injection of chlorhexidine (CHX) solution containing 0.1% CHX gluconate and 15% ethanol for 4 wk. The rats in the treatment group were treated with HL156A (1 mg·kg(-1)·day(-1)). Control rats were injected with vehicle alone. In vitro, cultured rat peritoneal mesothelial cells (RPMCs) were treated with either high glucose (HG; 50 mM), normal glucose (NG; 5 mM), NG+HL156A, or HG+HL156A. HL156A in supplemented rats ameliorated peritoneal calcification, cocoon formation, bowel obstruction, and PF. Immunohistochemistry showed reduced fibronectin accumulation in the peritoneum of HL156A-treated rats compared with those injected with CHX alone. HL156A treatment of RPMCs inhibited HG-induced myofibroblast transdifferentiation and markers of epithelial-mesenchymal transition (EMT). Moreover, HL156A ameliorated HG-induced transforming growth factor-ß1, Smad3, Snail, and fibronectin expression in the RPMCs via AMPK upregulation. These results suggest that HL156A exhibits a protective effect in PF progression. Further research is warranted to seek the therapeutic potential of HL156A as an antifibrotic agent in peritoneal dialysis patients.