Chronic Kidney Disease Stages G3b Research Articles

Effectiveness and Safety of Sodium-Glucose Cotransporter-2 Inhibitor Continuation in Patients With Type 2 Diabetes and Late-Stage Chronic Kidney Disease.

Background: Expansion of sodium-glucose cotransporter-2 inhibitor (SGLT2i) use in chronic kidney disease (CKD) prompted a pragmatic study of their safety and effectiveness in patients with type 2 diabetes mellitus (T2DM) and late-stage CKD. Objective: The primary clinical endpoint was change in HbA1c. Secondary clinical endpoints included change in body weight and blood pressure. Safety endpoints included kidney function indices, mycotic or urinary tract infection, acute kidney injury, dehydration, and ketoacidosis. Methods: Adult patients with T2DM and late-stage CKD prescribed an SGLT2i between June 1, 2018 and June 1, 2023 were included in this retrospective cohort study. Late-stage CKD was defined as CKD stage G3b, G4, or G5, including requiring dialysis or kidney transplantation. Endpoints were compared between patients who continued an SGLT2i versus those who discontinued. Results: Fifty-nine patients were included. Short-term follow-up over 4.2 ± 1.7 months revealed no difference in HbA1c between groups. Extended follow-up in a truncated sample over 10.4 ± 2.6 months showed modest, yet significantly lower HbA1c with continuation (median: -0.3 vs 0.1%; P = 0.04). Weight loss was greater when treatment continued (median: -1.8 vs 0.2 kg; P = 0.01), whereas blood pressure did not differ. No differences in safety endpoints were observed. Kidney function mildly, but significantly worsened with continuation (median estimated glomerular filtration rate [eGFR]: -2.7 vs 0 mL/min/1.73 m2; P = 0.03). Conclusions: Patients with T2DM and late-stage CKD had similar glucose control and safety profiles irrespective of SGLT2i continuation or discontinuation. This may favor clinical decision-making toward benefits of SGLT2i reduction in weight, cardiovascular events, CKD progression, and hospitalizations over potential safety concerns in these patients.

Physical activity and renal outcome in diabetic and non-diabetic patients with chronic kidney disease stage G3b to G5

The association of physical activity with renal outcome and mortality in advanced chronic kidney disease (CKD; i.e., estimated glomerular filtration rate [eGFR] < 45 ml/min/1.73m2) is poorly studied. We examined this association in patients with advanced CKD in Japan. We used the Rapid Assessment of Physical Activity to assess baseline physical activity and classify patients as active or inactive. CKD progression was defined as 40% decline in eGFR, eGFR < 10, or requiring dialysis or transplantation. Among the 1,808 eligible patients, after adjusting for possible confounders, hazard ratios (HRs) for poor renal outcome in the active group were 0.68 (95% CI, 0.44–1.04), 1.09 (0.86–1.38), and 1.01 (0.82–1.25) in CKD stage G3b, G4, and G5, respectively, suggesting a renal benefit of exercise in CKD stage G3b. Adjusted HRs for death were 0.79 (0.40–1.57), 0.55 (0.38–0.80), and 0.75 (0.44–1.26) in stage G3b, G4, and G5, respectively. While the adjusted HRs of death were 0.84 (0.52–1.38) and 0.60 (0.43–0.83) in diabetic and non-diabetic patients, suggesting that exercise may reduce mortality in non-diabetic patients. Our study suggests that exercise is associated with better survival in non-diabetic patients with CKD stage G3b-5, and better renal outcome in diabetic and non-diabetic CKD stage G3b.

Cost-Effectiveness of Empagliflozin in CKD with or without Albuminuria.

Background: The Study of Heart and Kidney Protection with Empagliflozin (EMPA-KIDNEY) expanded the chronic kidney disease (CKD) population that may benefit from sodium glucose co-transporter 2 (SGLT2) inhibitors in terms of estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). This enables the cost-effectiveness analysis of empagliflozin in subgroups stratified by these two parameters. Methods: A cost-utility analysis using the Markov model was performed to evaluate the cost-effectiveness of adding empagliflozin to the standard treatment for CKD in Japan over 20 years of observation. Each cohort with the initial eGFR (≥45 but &lt;60 ml/min per 1.73 m2, ≥30 but &lt;45 ml/min per 1.73 m2, or ≥20 but &lt;30 ml/min per 1.73 m2) and UACR (&lt;30 mg/g, ≥30 but &lt;300 mg/g, or ≥300 mg/g) within the defined ranges was analyzed. The changes in eGFR were determined based on the EMPA-KIDNEY study. An incremental cost-effectiveness ratio (ICER) of &lt;¥5,000,000 (approximately $35,500) per quality-adjusted life-year (QALY) was considered cost-effective. One-way deterministic analyses, probabilistic sensitivity analyses and scenario analyses were conducted to ensure the robustness of the results. Results: The addition of empagliflozin to standard treatment was associated with lower costs and higher QALYs in the macroalbuminuria or microalbuminuria cohorts, while the ICERs in the negative albuminuria cohorts were &gt;\5,000,000 per QALY, regardless of the initial eGFR. The probabilities of empagliflozin being cost-effective were &gt;84% in the macroalbuminuria or microalbuminuria cohorts but &lt;30% in the negative albuminuria cohorts. Scenario analyses where empagliflozin suppressed the eGFR decline in the negative albuminuria cohorts showed that the drug was cost-effective in CKD stage G3b and G4 cohorts. Empagliflozin was not cost-effective in patients with CKD stage G3a and microalbuminuria with the observation period of 10 years. Conclusion: In patients meeting the enrollment criteria for the EMPA-KIDNEY trial, the addition of empagliflozin to the standard treatment of CKD was judged as cost-effective for patients with albuminuria but not for those without albuminuria in Japanese healthcare system.

Impact of Serum Indoxyl Sulfate on One-Year Adverse Events in Chronic Kidney Disease Patients with Heart Failure.

Background/Objectives: Indoxyl sulfate, a uremic toxin, is associated with mortality and cardiovascular events in patients with chronic kidney disease (CKD). This study aimed to evaluate the prognostic implications of serum indoxyl sulfate levels in patients with heart failure and CKD. Methods and Results: This was a prospective multicenter observational study. Overall, 300 patients with chronic heart failure with a previous history of hospitalization and an estimated glomerular filtration rate (eGFR) of 45 mL/min/1.73 m2 or less (CKD stage G3b to G5) without dialysis were analyzed. The primary outcome assessed in a time-to-event analysis from the measurement of indoxyl sulfate was a composite of all-cause death, hospitalization for heart failure, nonfatal myocardial infarction, and nonfatal stroke. Clinical events were followed-up to one year after indoxyl sulfate measurement. The median patient age was 75 years, and 57% of the patients were men. We divided the cohort into low and high indoxyl sulfate categories according to a median value of 9.63 mg/mL. The primary outcome occurred in 27 of 150 patients (18.0%) in the low indoxyl sulfate group and 27 of 150 patients (18.0%) in the high indoxyl sulfate group (hazard ratio, 1.00; 95% confidence interval, 0.58 to 1.70, p = 0.99). In the post hoc exploratory analyses, the results were consistent across age, sex, body mass index, left ventricular ejection fraction, eGFR, and N-terminal pro b-type natriuretic peptide. Conclusions: Among heart failure patients with CKD stages G3b to 5G, serum indoxyl sulfate concentrations were not significantly associated with the subsequent occurrence of cardiovascular events.

Progressive Kidney Failure by Angiotensinogen Inactivation in the Germline.

Autosomal recessive renal tubular dysgenesis is a rare, usually fatal inherited disorder of the renin-angiotensis system (RAS). Herein, we report an adolescent individual experiencing an unknown chronic kidney disease and aim to provide novel insights into disease mechanisms. Exome sequencing for a gene panel associated with renal disease was performed. The RAS was assessed by comprehensive biochemical analysis in blood. Renin expression was determined in primary tubular cells by quantitative polymerase chain reaction and in situ hybridization on kidney biopsy samples. Allele frequencies of heterozygous and biallelic deleterious variants were determined by analysis of the Genomics England 100,000 Genomes Project. The patient was delivered prematurely after oligohydramnios was detected during pregnancy. Postnatally, he recovered from third-degree acute kidney injury but developed chronic kidney disease stage G3b over time. Exome sequencing revealed a previously reported pathogenic homozygous missense variant, p.(Arg375Gln), in the AGT (angiotensinogen) gene. Blood AGT concentrations were low, but plasma renin concentration and gene expression in kidney biopsy, vascular, and tubular cells revealed strong upregulation of renin. Angiotensin II and aldosterone in blood were not abnormally elevated. Renal tubular dysgenesis may present as chronic kidney disease with a variable phenotype, necessitating broad genetic analysis for diagnosis. Functional analysis of the RAS in a patient with AGT mutation revealed novel insights regarding compensatory upregulation of renin in vascular and tubular cells of the kidney and in plasma in response to depletion of AGT substrate as a source of Ang II (similarly observed with hepatic AGT silencing for the treatment of hypertension).

Major adverse kidney events in multidisciplinary chronic kidney disease care compared with usual outpatient care: a propensity score matched analysis.

Chronic kidney disease (CKD) is a public health problem worldwide. Multidisciplinary care has been recommended in clinical practice to delay disease progression and minimize complications. However, the effectiveness of multidisciplinary care on major adverse kidney events in CKD patients is still inconclusive. We conducted a cohort study in patients with CKD stages G3b to 4 who were followed up at Bhumibol Adulyadej Hospital from 2014 to 2020. Propensity score matching by age, sex, CKD staging, Diabetes Mellitus (DM), blood pressure and rate of estimated Glomerular Filtration Rate (eGFR) decline before inclusion between patients in multidisciplinary CKD care (MDC) and usual outpatient care (UOC) was performed. The primary outcome was a composite of cardiovascular or renal mortality, 40% eGFR decline and initiation of long-term kidney replacement therapy. After 1:1 propensity score matching, 822 patients were included. Mean age was 70.9years, 64% had diabetes. During the mean follow-up of 3.3years, rate of reaching the primary endpoint was lower in the multidisciplinary CKD care group than in the usual outpatient care group (24.1% vs. 38.9%; hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.52-0.86; P = 0.002). The multidisciplinary CKD care group benefited more than the usual outpatient care group with regard to 40% eGFR decline (21.7% vs. 35.0%; HR, 0.67; 95%CI 0.52-0.88; P = 0.004), all-cause mortality (8.5% vs. 19.5%; HR, 0.60; 95%CI 0.40-0.90; P = 0.014), non-cardiovascular death (6.1% vs. 15.1%; HR, 0.56; 95%CI 0.35-0.90; P = 0.015) and hospitalizations per year (1.0 ± 1.5 vs. 1.6 ± 2.0; P < 0.001). According to subgroup analysis, diabetes mellitus patients benefited the most from multidisciplinary CKD care. In a tertiary care hospital, multidisciplinary CKD care showed benefits over usual outpatient care on kidney outcomes in patients with CKD stages G3b and 4. The benefit was enhanced in DM patients.

Risk factor for progression to kidney failure with replacement therapy in elderly patients with chronic kidney disease: A retrospective single‐centre cohort study

Although the number of elderly patients with chronic kidney disease (CKD) has increased, few studies have examined their prognosis. The study design was a retrospective cohort study at a single centre. We evaluated 301 patients aged ≥75 years old with CKD stage G3a to G5. The primary endpoint was kidney failure with replacement therapy (KFRT) and secondary endpoints were all-cause mortality and annual decline rates of estimated glomerular filtration rate (eGFR). The incidence of KFRT was estimated using the cumulative incidence method considering the competing risk of death. To identify the independent risk factors related to KFRT, multivariate Fine-Gray regression model analysis were performed. The median age of the patients was 79 years and the median eGFR was 24.0 mL/min/1.73 m2 at baseline. Urinary protein was positive in 70% of patients. With a median follow-up of 24.5 months, 35% of the patients developed KFRT and 9% died. Kidney survival significantly decreased according to the CKD stage at baseline. In patients without proteinuria, the cumulative incidence of KFRT increased in CKD stage G5 patients, while in patients with proteinuria, the incidence of KFRT increased from patients with CKD stage G3b. Multivariate Fine-Gray regression model revealed that less aged, CKD stage G5, baseline data such as proteinuria, hypoalbuminemia, hyperphosphatemia, and hyperuricemia were independent risk factors for KFRT. Elderly CKD patients with proteinuria need to be carefully monitored even at an early CKD stage because of the risk of developing KFRT.

Frequency and predictors of inappropriate medication dosages for cardiovascular disease prevention in chronic kidney disease patients: A retrospective cross-sectional study in a Malaysian primary care clinic

Patients with chronic kidney disease (CKD) are at increased risk of cardiovascular events. This study aimed to assess the frequency of inappropriate medication dosages (IMD) for cardiovascular disease prevention among patients with CKD and its predictors in an urban academic primary care clinic in Selangor, Malaysia. All patients who attended the clinic from April to June 2019 and fulfilled the inclusion criteria were included in this cross-sectional study, except for those with an estimated glomerular filtration rate (eGFR) of more than 90 ml/min, diagnosed with urinary tract infection, pregnant or were on dialysis for end stage renal disease. Their prescriptions on the electronic medical record (EMR) system were evaluated for appropriateness using the dose adjustment recommendations based on the 2018 Malaysian Clinical Practice Guidelines on management of CKD. A total of 362 medical records were included in this study. 16.6% (95% Confidence Interval [CI]: 12.9–20.8) or 60 out of 362 of the patient records analysed contained medications prescribed with inappropriate dosages. Patients with higher stages of CKD were associated with higher odds of IMD, namely CKD stage G3b (adjusted Odds Ratio [aOR] 10.41; 95% CI: 2.31–46.88) and CKD stage 4–5 (aOR 15.76; 95% CI: 3.22–77.28). Other predictors of IMD were diagnosis of diabetes mellitus (aOR 6.40; 95% CI: 2.15–19.01), number of prescribed medications of 5 or more (aOR 4.69; 95% CI: 1.55–14.20), and eGFR reduction of more than 25% over one year (aOR 2.82; 95% CI: 1.41–5.65). Within the limitations of this study, we conclude that the occurrence of IMD for CVD prevention was low in CKD patients in this primary care clinic. Medications with inappropriate dosages identified in this study include simvastatin, fenofibrate, hydrochlorothiazide, spironolactone, metformin, gliclazide, sitagliptin, dapagliflozin and empagliflozin. Clinicians should consider the predictors of inappropriate medication dosages listed above when prescribing to patients with CKD to reduce the risk of medications-related toxicities and adverse effects. Limitations of this study should be considered when interpreting the findings presented.

Ureteral Obstruction Due to Inadvertent Placement of the Suprapubic Catheter and Bladder Indwelling Catheter: Presentation of Two Clinical Cases and Review of the Literature

Introduction: Suprapubic catheter (SPC) and bladder indwelling catheter (BIC) placement are among the most common urological procedures. Inadvertent misplacement of the catheter tip into the ureteral orifice is an infrequent event with potentially critical complications. Case Presentation: We describe two cases of inadvertent intraureteral misplacement of an SPC and a BIC. A 66-year-old man with chronic kidney disease (CKD) stage G3b, urethral stenosis, long-term SPC who attended the emergency room (ER) 6 hours after the last catheter replacement due to low back pain, fever, deterioration of the general condition, anuria, acute kidney injury (AKI); CT-scan revealed a left uretero-hydronephrosis secondary to obstruction of the catheter balloon misplaced inside the distal ureter. A 59-year-old woman with CKD stage G3b, post-radiotherapy cystitis, and small capacity bladder, long-term BIC who attended the ER a few hours after the last BIC replacement due to abdominal pain, anuria, AKI; CT-scan revealed left hydronephrosis secondary to catheter obstruction within the distal ureter. In both patients, management was conservative, consisting of removing the catheter and repositioning it inside the bladder, in addition to hydration and antibiotherapy. Conclusions: These cases illustrate that awareness of this rare complication can be prevented by confirming the correct positioning of SPC or BIC after its replacement. Early detection and management of this complication can prevent a serious clinical setting.

Continuous Glucose Monitoring Metrics in the Assessment of Glycemia in Moderate-to-Advanced CKD in Diabetes

IntroductionGlycated hemoglobin A1c (HbA1c) has reduced reliability in advanced chronic kidney disease (CKD) owing to factors influencing red cell turnover. Recent guidelines support the use of continuous glucose monitoring (CGM) in glycemic assessment in these patients. We evaluated relationships between HbA1c and CGM metrics of average glycemia and glucose variability (GV) in moderate-to-advanced CKD.MethodsThere were a total of 90 patients with diabetes in CKD stages G3b (n = 33), G4 (n = 43), and G5 (nondialysis) (n = 14) (age [mean ± SD] 65.4 ± 9.0 years, estimated glomerular filtration rate [eGFR] 26.1 ± 9.6 ml/min per 1.73 m2, and HbA1c 7.4 ± 0.8%). CGM metrics were estimated from blinded CGM (Medtronic Ipro2 with Enlite sensor) and compared with HbA1c in the same week.ResultsCorrelations between glucose management indicator (GMI) and HbA1c attenuated with advancing CKD (G3b [r = 0.68, P < 0.0001], G4 [r = 0.52, P < 0.001], G5 [r = 0.22, P = 0.44], P = 0.01 for CKD stage). In G3b and G4, HbA1c correlated significantly with time-in-range (TIR) (3.9–10.0 mmol/l) (r = −0.55 and r = −0.54, respectively) and % time > 13.9 mmol/l (r = 0.53 and r = 0.44, respectively), but not in G5. HbA1c showed no correlation with % time <3.0 mmol/l (r = −0.045, P = 0.67) or % coefficient of variation (CV) (r = −0.05, P = 0.64) in any CKD stage. Only eGFR was a significant determinant of bias for the difference between GMI and HbA1c (difference −0.28%, 95% CI [−0.52 to −0.03] per 15 ml/min per 1.73 m2 decrement, P = 0.03).ConclusionCGM-derived indices might serve as an adjunct to HbA1c monitoring to guide glycemic management, especially in those with eGFR <30 ml/min per 1.73 m2. Time in hypoglycemia and glycemic variability are relevant glycemic targets for optimization not reflected by HbA1c.

Inflammation and physical dysfunction: responses to moderate intensity exercise in chronic kidney disease.

People with chronic kidney disease (CKD) experience skeletal muscle wasting, reduced levels of physical function and performance, and chronic systemic inflammation. While it is known that a relationship exists between inflammation and muscle wasting, the association between inflammation and physical function or performance in CKD has not been well studied. Exercise has anti-inflammatory effects, but little is known regarding the effect of moderate intensity exercise. This study aimed to (i) compare systemic and intramuscular inflammation between CKD stage G3b-5 and non-CKD controls; (ii) establish whether a relationship exists between physical performance, exercise capacity and inflammation in CKD; (iii) determine changes in systemic and intramuscular inflammation following 12 weeks of exercise; and (iv) investigate whether improving inflammatory status via training contributes to improvements in physical performance and muscle mass. This is a secondary analysis of previously collected data. CKD patients stages G3b-5 (n=84, n=43 males) and non-CKD controls (n=26, n=17 males) underwent tests of physical performance, exercise capacity, muscle strength and muscle size. In addition, a subgroup of CKD participants underwent 12 weeks of exercise training, randomized to aerobic (AE, n=21) or combined (CE, n=20) training. Plasma and intramuscular inflammation and myostatin were measured at rest and following exercise. Tumour necrosis factor-α was negatively associated with lower $^{^{^{.}}}{\rm V}$O2Peak (P=0.01), Rectus femoris-cross sectional area (P=0.002) and incremental shuttle walk test performance (P<0.001). Interleukin-6 was negatively associated with sit-to-stand 60 performances (P=0.006) and hand grip strength (P=0.001). Unaccustomed exercise created an intramuscular inflammatory response that was attenuated following 12 weeks of training. Exercise training did not reduce systemic inflammation, but AE training did significantly reduce mature myostatin levels (P=0.02). Changes in inflammation were not associated with changes in physical performance. Systemic inflammation may contribute to reduced physical function in CKD. Twelve weeks of exercise training was unable to reduce the level of chronic systemic inflammation in these patients, but did reduce plasma myostatin concentrations. Further research is required to further investigate this.

Prevalences of hyperuricemia and electrolyte abnormalities in patients with chronic kidney disease in Japan: A nationwide, cross-sectional cohort study using data from the Japan Chronic Kidney Disease Database (J-CKD-DB).

BackgroundThe Japan Chronic Kidney Disease Database (J-CKD-DB) is a nationwide clinical database of patients with chronic kidney disease (CKD) based on electronic health records. The objective of this study was to assess the prevalences of hyperuricemia and electrolyte abnormalities in Japanese patients with CKD.MethodsIn total, 35,508 adult outpatients with estimated glomerular filtration rates of 5–60 ml/min/1.73 m2 in seven university hospitals were included this analysis. The proportions of patients with CKD stages G3b, G4, and G5 were 23.5%, 7.6%, and 3.1%, respectively.ResultsLogistic regression analysis showed that prevalence of hyperuricemia was associated with CKD stages G3b (adjusted odds ratio [95% confidence interval]: 2.12 [1.90–2.37]), G4 (4.57 [3.92–5.32]), and G5 (2.25 [1.80–2.80]). The respective prevalences of hyponatremia, hypercalcemia, hyperphosphatemia, and narrower difference between serum sodium and chloride concentrations were elevated in patients with CKD stages G3b, G4, and G5, compared with those prevalences in patients with CKD stage G3a. The prevalences of hyperkalemia were 8.3% and 11.6% in patients with CKD stages G4 and G5, respectively. In patients with CKD stage G5, the proportions of patients with optimal ranges of serum uric acid, potassium, corrected calcium, and phosphate were 49.6%, 73.5%, 81.9%, and 56.1%, respectively.ConclusionsWe determined the prevalences of hyperuricemia and electrolyte abnormalities in Japanese patients with CKD using data from a nationwide cohort study.

Prevalence of anemia in patients with chronic kidney disease in Japan: A nationwide, cross-sectional cohort study using data from the Japan Chronic Kidney Disease Database (J-CKD-DB).

BackgroundThe Japan Chronic Kidney Disease Database (J-CKD-DB) is a nationwide clinical database of patients with chronic kidney disease (CKD) based on electronic health records. The objective of this study was to assess the prevalence of anemia and the utilization rate of erythropoiesis-stimulating agents (ESAs) in Japanese patients with CKD.MethodsIn total, 31,082 adult outpatients with estimated glomerular filtration rates of 5–60 ml/min/1.73 m2 in seven university hospitals were included this analysis. The proportions of patients with CKD stages G3b, G4, and G5 were 23.5%, 7.6%, and 3.1%, respectively.ResultsThe mean (standard deviation) hemoglobin level of male patients was 13.6 (1.9) g/dl, which was significantly higher than the mean hemoglobin level of female patients (12.4 (1.6) g/dl). The mean (standard deviation) hemoglobin levels were 11.4 (2.1) g/dl in patients with CKD stage G4 and 11.2 (1.8) g/dl in patients with CKD stage G5. The prevalences of anemia were 40.1% in patients with CKD stage G4 and 60.3% in patients with CKD stage G5. Logistic regression analysis showed that diagnoses of CKD stage G3b (adjusted odds ratio [95% confidence interval]: 2.32 [2.09–2.58]), G4 (5.50 [4.80–6.31]), and G5 (9.75 [8.13–11.7]) were associated with increased prevalence of anemia. The utilization rates of ESAs were 7.9% in patients with CKD stage G4 and 22.4% in patients with CKD stage G5.ConclusionsWe determined the prevalence of anemia and utilization rate of ESAs in Japanese patients with CKD using data from a nationwide cohort study.

Medical and Dental Visits of Chronic Kidney Disease-Diagnosed Participants Analyzed From the Specific Health Checkups Results in Japan: TAMA MED Project-CKD.

BackgroundSince 2012, Tama City has promoted the early detection of chronic kidney disease (CKD), through an initiative that measures serum creatinine as part of the specific health checkups. We examined preventive measures against CKD deterioration based on the outcomes of this initiative.MethodsThe complications, medication status, body mass index, smoking status and other determining factors were surveyed among CKD-diagnosed participants over 3 years between 2013 and 2015. Moreover, factors aggravating CKD were investigated via a survey of medical and dental visits based on health insurance claim data over the same period.ResultsThere was an increased rate of comorbid hypertension with each increase in the CKD stage. Comorbidity rates of diabetes mellitus, dyslipidemia, obesity, and smoking increased until CKD stage G4, and then decreased from stage G5. A substantial number of participants with CKD stage G3b and above were not medicated despite comorbidities like hypertension, diabetes mellitus and dyslipidemia. While the rate of regular visits at medical institutions was seen to increase significantly in accordance with the worsening degree of CKD, there were also individuals who, despite having severe CKD, did not visit medical institutions specializing in internal medicine. The rate of dental visits decreased as the CKD stage increased, and further decreased as the diabetic control status worsened.ConclusionsCKD patients should become aware of the importance of the dental visit because only a limited number of patients with advanced CKD received dental care.

A 91-year-old woman with severe aortic stenosis successfully underwent maintenance hemodialysis via arteriovenous fistula after transcatheter aortic valve implantation: a case report with literature review

BackgroundTranscatheter aortic valve implantation (TAVI) has evolved to be a treatment of choice in high-risk patients with aortic stenosis (AS). However, it is not known whether TAVI is safe and beneficial for the creation of arteriovenous fistula for maintenance hemodialysis in high-risk patients with severe AS.Case presentationA 91-year-old woman was referred to our hospital due to oligoanuria and progressive renal dysfunction. She was diagnosed with anti-glomerular basement membrane (GBM) disease. She had hypertension, chronic kidney disease stage G3b, and AS. We chose not to perform immunosuppressive therapy and plasmapheresis for anti-GBM disease because the risk of death outweighed the benefit of treatment. Hemodialysis with a venous catheter was initiated for the renal indication. As she showed severe AS, she had a risk of cardiac decompensation after arteriovenous fistula creation for dialysis. Following the clinical decision-making process, she underwent TAVI. Although she required the implantation of a cardiac pacemaker for an advanced atrioventricular block that occurred 11 days after TAVI, arteriovenous fistula was successfully created thereafter. She could undergo maintenance hemodialysis using arteriovenous fistula.ConclusionsTAVI is safe and beneficial for the creation of arteriovenous fistula shortly after initiating acute hemodialysis using a catheter in a very old patient with anti-GBM disease.

Changes in Serum and Urinary Potassium Handling Associated with Renin-Angiotensin-Aldosterone System Inhibitors in Advanced Chronic Kidney Disease Patients.

ObjectiveThis study aimed to (i) compare the extent of urinary potassium (K+) excretion in addition to the changes in serum K+ concentration: and (ii) clarify the association between changes in serum K+ concentration, urinary K+ excretion, and acid-base status with or without renin-angiotensin-aldosterone system (RAAS) inhibitors in patients with advanced chronic kidney disease (CKD) stages.MethodsSix hundred and ninety-one patients with advanced CKD (CKD G3b, 161; G4, 271; G5, 259) were retrospectively evaluated. Differences in serum K+ concentration, urinary K+ excretion, and serum sodium and chloride differences (Na+−Cl-) were compared among patients with RAAS inhibitors, RAAS inhibitors and diuretic agents, and without either medication in each CKD stage.ResultsSerum K+ concentrations in patients with RAAS inhibitors were significantly higher than in those with RAAS inhibitors and diuretics in CKD stage G3b and the other two treatment groups in CKD stage G4. Urinary K+ excretion among the three groups did not differ significantly in each CKD stage. Serum Na+−Cl- differences in patients with RAAS inhibitors were significantly smaller than in those with RAAS inhibitors and diuretics in CKD stages G3b (p = 0.006) and the other two groups in CKD stage G4 (vs. RAAS inhibitors and diuretics, p <0.001; vs. without either medication, p = 0.008).ConclusionOur study demonstrated that RAAS inhibitor use might be associated with hyperkalemia via not decreased urinary K+ excretion but rather K+ redistribution from intracellular to extracellular fluid induced by the progression of metabolic acidosis in patients with advanced CKD, particularly stages G3b and G4.

Patterns of medication use and the burden of polypharmacy in patients with chronic kidney disease: the German Chronic Kidney Disease study.

BackgroundPatients with chronic kidney disease (CKD) bear a substantial burden of comorbidities leading to the prescription of multiple drugs and a risk of polypharmacy. However, data on medication use in this population are scarce.MethodsA total of 5217 adults with an estimated glomerular filtration rate (eGFR) between 30 and 60 mL/min/1.73 m2 or an eGFR ≥60 mL/min/1.73m2 and overt proteinuria (>500 mg/day) were studied. Self-reported data on current medication use were assessed at baseline (2010–12) and after 4 years of follow-up (FU). Prevalence and risk factors associated with polypharmacy (defined as the regular use of five or more drugs per day) as well as initiation or termination of polypharmacy were evaluated using multivariable logistic regression.ResultsThe prevalence of polypharmacy at baseline and FU was almost 80%, ranging from 62% in patients with CKD Stage G1 to 86% in those with CKD Stage G3b. The median number of different medications taken per day was eight (range 0–27). β-blockers, angiotensin-converting enzyme inhibitors and statins were most frequently used. Increasing CKD G stage, age and body mass index, diabetes mellitus, cardiovascular disease and a history of smoking were significantly associated with both the prevalence of polypharmacy and its maintenance during FU. Diabetes mellitus was also significantly associated with the initiation of polypharmacy [odds ratio (OR) 2.46, (95% confidence interval 1.36–4.45); P = 0.003].ConclusionMedication burden in CKD patients is high. Further research appears warranted to address the implications of polypharmacy, risks of drug interactions and strategies for risk reduction in this vulnerable patient population.

Serum levels of miR-126 and miR-223 and outcomes in chronic kidney disease patients

Several microRNAs (miRNAs) have been linked to chronic kidney disease (CKD) mortality, cardiovascular (CV) complications and kidney disease progression. However, their association with clinical outcomes remains poorly evaluated. We used real-time qPCR to measure serum levels of miR-126 and miR-223 in a large cohort of 601 CKD patients (CKD stage G1 to G5 patients or on renal replacement therapy – CKD G5D) from Ghent University Hospital and 31 healthy controls. All-cause mortality and cardiovascular and renal events were registered as endpoints over a 6 year follow-up period. miR-126 levels were significantly lower from CKD stage G2 on, compared to controls. The serum levels of miR-223 were significantly lower from CKD stage G3B on. When considering overall mortality, patients with levels of either miR-126 or miR-223 below the median had a lower survival rate. Similar results were observed for CV and renal events. The observed link between the two miRNAs’ seric levels and mortality, cardiovascular events or renal events in CKD appears to depend on eGFR. However, this does not preclude their potential role in the pathophysiology of CKD. In conclusion, CKD is associated with a decrease in circulating miR-223 and miR-126 levels.

Safety and efficacy of daclatasvir and asunaprevir in hepatitis C virus-infected patients with renal impairment.

Hepatitis C virus (HCV) infection is a risk factor for end-stage renal disease, renal graft failure, and hemodialysis patient mortality. However, the efficacy of direct-acting antiviral therapy for HCV-infected patients with renal impairment is unclear. Additionally, the promising NS5B inhibitor sofosbuvir has not been recommended for patients with severe renal impairment. In this prospective, multicenter study, we evaluated the efficacy and safety of daclatasvir and asunaprevir combination therapy, with a focus on patients with renal impairment. The study included 322 genotype 1 HCV-infected patients who received daclatasvir and asunaprevir combination therapy. The safety and sustained virological response was examined at 12weeks after the end of treatment and safety was evaluated according to renal function. Of 322 patients, 5% (16/322) and 2.5% (8/322) had chronic kidney disease stage G3b (estimated glomerular filtration rate [eGFR], 30-44mL/min/1.73m2 ) and stage G4/5 (eGFR, 15-29/<15mL/min/1.73m2 ), respectively. Baseline presence of the NS5A resistance-associated variant, previous simeprevir treatment, and HCV RNA titers, which were predictors of a sustained viral response, were similar between patients with eGFR <45mL/min/1.73m2 and eGFR >45mL/min/1.73m2 . Notably, the 12-week sustained viral response rate was comparable in patients with eGFR <45mL/min/1.73m2 (100%, 24/24) and those with eGFR >45mL/min/1.73m2 (88.9%, 265/298; P = 0.07). Treatment discontinuation rates and adverse events, including alanine aminotransferase elevation, anemia, and renal disorders, were similar between the two groups. Daclatasvir and asunaprevir combination therapy for patients with renal dysfunction was highly effective and safe.

Analysis of factors affecting rehospitalization of patients with chronic kidney disease after educational hospitalization.

BackgroundChronic kidney disease (CKD) is associated with a high risk of cardiovascular disease complications. Therefore, medical institutions conduct educational hospitalization for early treatment and education of CKD patients. However, patients who have been discharged after achieving educational targets can end up showing poor symptoms at home. There also have been several cases of rehospitalization or disease aggravation. In this study, we analyzed rehospitalized patients who were discharged from the hospital after CKD educational hospitalization and investigated the purpose of analyzing rehospitalization factors.Materials and methodsThis was an observational case-control study conducted at Yokosuka Kyousai Hospital. We performed univariate analysis using patient background features and laboratory data between a rehospitalization group and a no-rehospitalization group. Next, we performed multiple logistic regression analysis using the results of the univariate analysis.ResultsFrom the results of this study, we identified independent risk factors, such as serum albumin level, heart-failure complications, and estimated glomerular filtration rate (eGFR). Moreover, the serum Alb level was identified as the most important risk factor for rehospitalization. Therefore, we considered that it is important to live a life that makes it possible to maintain CKD stage G3b for a long time after discharge, because the cutoff level of eGFR is 31 mL/minute/1.73 m2.ConclusionWe believe that it is important to educate patients, their families, and medical staff on the importance of early detection and treatment, and we consider that this approach is important to inclusively protect the kidney.