Indoxyl Sulfate Might Play a Role in Sarcopenia, While Myostatin Is an Indicator of Muscle Mass in Patients with Chronic Kidney Disease: Analysis from the RECOVERY Study.

Serum myostatin and indoxyl sulfate (IS) levels increase with kidney function decline and may function as uremic toxins in chronic kidney disease (CKD)-related sarcopenia. Herein, we analyzed the association between serum myostatin and IS levels and sarcopenia in patients with CKD, by performing a post hoc analysis of baseline data extracted from the RECOVERY study (clinicaltrials.gov: NCT03788252) of 150 patients with CKD. We stratified patients into two groups according to the median value of myostatin (cutoff 4.5 ng/mL) and IS levels (cutoff 0.365 mg/dL). The proportion of patients with sarcopenia was higher in those with high IS levels but lower in those with high myostatin levels. The skeletal muscle mass index (SMI) and handgrip strength (HGS) were significantly lower in patients with high IS levels but significantly higher in patients with high myostatin levels. IS levels showed a negative correlation with glomerular filtration rate (GFR), SMI, and HGS. However, myostatin levels were positively correlated with SMI and HGS, but not with GFR. Sarcopenia was independently associated with age and IS level after adjustment. Increased levels of serum total IS might play a role in sarcopenia, while increased levels of serum myostatin are associated with muscle mass in patients with CKD.

Effects of AST-120 on muscle health and quality of life in chronic kidney disease patients: results of RECOVERY study.

BACKGROUND: The prevalence of sarcopenia is increased with declining renal function. Elevated serum indoxyl sulfate levels are associated with poor skeletal muscle conditions. We aimed to determine the effects of AST-120, the oral adsorbent of indoxyl sulfate, on sarcopenia and sarcopenia-associated factors in chronic kidney disease patients. METHODS: This was a 48 week, randomized controlled, parallel group, open-label, multicentre trial (n = 150). The participants were randomly assigned in a 1:1 ratio to the control (CON) and AST-120 (Renamezin®, REN) groups. Outcome measurements were performed at baseline and every 24 weeks for 48 weeks. The primary outcome was gait speed difference ≥0.1 m/s between the two groups, and secondary outcomes included hand grip strength, muscle mass, and health-related quality of life. RESULTS: A difference of gait speed ≥0.1 m/s was not observed during the study period. The mean dynamic-start gait speed in the REN group increased from baseline to 48 weeks (1.04 ± 0.31 to 1.08 ± 0.32 m/s, P = 0.019). The static-start gait speed changed by -0.024 and 0.04 m/s (P = 0.049) in the CON and REN groups over 48 weeks, respectively. Hand grip strength decreased during the first 24 weeks and did not significantly change over the next 24 weeks in either group. The proportion of low muscle mass or sarcopenia at baseline was larger in the REN group than in the CON group, but the difference attenuated over the study period [low muscle mass and sarcopenia in the CON and REN groups at baseline, 4.0% vs. 18.9% (P = 0.004) and 2.7% vs. 13.5% (P = 0.017); at 24 weeks, 2.9% vs. 13.6% (P = 0.021) and 1.4% vs. 10.5% (P = 0.029); and at 48 weeks, 7.6% vs. 12.9% (P = 0.319) and 4.5% vs. 8.1% (P = 0.482), respectively]. Bodily pain, vitality, symptoms/problems, and cognitive function in the REN group improved, while the quality of social interactions and the kidney disease effects in the CON group aggravated from baseline to 48 weeks. Interaction between time and group was evident only in symptoms/problems, cognitive function, and kidney disease effects. CONCLUSIONS: The addition of AST-120 to standard treatment in chronic kidney disease patients did not make a significant difference in gait speed, although AST-120 modestly had beneficial effects on gait speed change and quality of life and showed the potential to improve sarcopenia. (clinicaltrials.gov: NCT03788252).

Light Chain Deposition Disease Associated With Multiple Myeloma Developing in Late Pregnancy.

Preeclampsia is the most common cause of proteinuria with hypertension during pregnancy. Primary kidney disease and kidney disease secondary to systemic disorders may rarely occur during pregnancy, resulting in proteinuria. A 34-year-old woman was admitted to our hospital with abdominal distention and lower extremity edema. The pregnancy was terminated at the 24th week of gestation due to preterm labor. Even after the delivery, proteinuria and renal deterioration continued to progress. The M-peak was not found on serum and urine protein electrophoresis. The serum free light chains assay showed absolute elevation of lambda chains at 1013.9 mg/L with a decreased kappa to lambda ratio of 0.05. Kidney biopsy revealed light chain deposition disease with lambda light chain deposits on immunofluorescence. Bone marrow examination was compatible with multiple myeloma. To our knowledge, this is the first reported case of light chain deposition disease associated with multiple myeloma during pregnancy.

Chronic asymptomatic pyuria precedes overt urinary tract infection and deterioration of renal function in autosomal dominant polycystic kidney disease.

BACKGROUND: Urinary tract infection (UTI) occurs in 30%-50% of individuals with autosomal dominant polycystic kidney disease (ADPKD). However, the clinical relevance of asymptomatic pyuria in ADPKD patients remains unknown. METHODS: We retrospectively reviewed medical records of 256 ADPKD patients who registered to the ADPKD clinic at Seoul National University Hospital from Aug 1999 to Aug 2010. We defined the asymptomatic pyuria as more than 5-9 white blood cells in high-power field with no related symptoms or signs of overt UTI. Patients were categorized into 2 groups depending on its duration and frequency: Group A included non-pyuria and transient pyuria patients; Group B included recurrent and persistent pyuria patients. The association between asymptomatic pyuria and both the development of overt UTI and the deterioration of renal function were examined. RESULTS: With a mean follow-up duration of 65.3 months, 176 (68.8%) out of 256 patients experienced 681 episodes of asymptomatic pyuria and 50 episodes of UTI. The annual incidence of asymptomatic pyuria was 0.492 episodes/patient/year. The patients in group B showed female predominance (58.5% vs. 42.0%, P=0.01) and experienced an upper UTI more frequently (hazard ratio: 4.612, 95% confidence interval: 1.735-12.258; P=0.002, adjusted for gender and hypertension). The annual change in estimated glomerular filtration rate (ΔeGFR) was significantly larger in magnitude in group B than in group A (-2.7±4.56 vs. -1.17±5.8, respectively; P=0.01). Age and Group B found to be the independent variables for ΔeGFR and developing end-stage renal disease (16.0% vs. 4.3%, respectively; P=0.001). CONCLUSIONS: Chronic asymptomatic pyuria may increase the risk of developing overt UTI and may contribute to declining renal function in ADPKD.