Prevalence and relevance of cachexia as diagnosed by two different definitions in patients undergoing hemodialysis: A retrospective and exploratory study.

OBJECTIVE: Cachexia is present in various chronic diseases and is associated with decreased quality of life and increased risk of morbidity and mortality. However, evidence regarding the association of cachexia with prognosis in patients undergoing hemodialysis is limited. We assessed cachexia using two definitions and compared prevalence, functional impairment, and prognostic impact in patients undergoing hemodialysis. METHODS: We enrolled outpatients undergoing hemodialysis at two centers retrospectively. We assessed cachexia using the conventional cachexia (Evans' criteria) and the Asian Working Group for Cachexia (AWGC) criteria. The study examined all-cause mortality and functional status (Clinical Frailty Scale and short physical performance battery). We used Cox proportional hazards model to examine the association with prognosis, and logistic regression analysis to examine the association with functional impairment. RESULTS: Among 367 patients (mean age, 67 years; 63 % male), cachexia prevalence, as defined by Evans' criteria and AWGC, was 21.3 % and 35.2 %, respectively. Cachexia as defined by Evans' criteria was associated with an increased risk of all-cause mortality (hazard ratio [HR], 95 % confidence interval [CI]: 1.81, 1.02-3.23). Also, cachexia as defined by AWGC criteria showed suggestive association with increasing mortality (HR, 95 % CI: 1.56, 0.90-2.70). Similar results were seen between cachexia and functional impairment. CONCLUSIONS: Among patients on hemodialysis, cachexia was highly prevalent and was associated with poor prognosis and functional impairment. Detecting cachexia in earlier stages may be useful for risk stratification in this population.

Association between Physical Frailty and Sleep Disturbances among Patients on Hemodialysis: A Cross-Sectional Study.

INTRODUCTION: Among patients on hemodialysis (HD), physical frailty and sleep disturbances are not only common but also associated with adverse outcomes. The aim of this study was to evaluate the association between physical frailty and sleep disturbances in patients on HD. METHODS: This cross-sectional study was conducted from June 2017 to March 2021, with outpatients receiving HD 3 times a week at two dialysis facilities in Japan. Sleep disturbances were identified with the Athens Insomnia Scale (AIS). Physical frailty was defined using the Fried Frailty Phenotype. Patients were classified as "non-frailty (number of frailty components: 0-2)" or "frailty (3-5)." We examined the association of sleep disturbances with physical frailty and its components by performing a logistic regression analysis. RESULTS: We analyzed 360 patients (mean age 65.6 years; 62% men). Eighty-one patients (23%) were classified into the group with frailty, and the mean AIS score was 5.2 ± 4.2 points. After adjusting for clinical characteristics, increasing the AIS score per 1 point was associated with higher odds of physical frailty (odds ratio, 1.12; 95% confidence interval, 1.05-1.20; p < 0.01). As for the frailty components, exhaustion, low physical activity, and weak grip strength showed an association with sleep disturbances (all p < 0.05). CONCLUSIONS: Sleep disturbances were independently associated with physical frailty in patients on HD. Future studies are warranted to investigate the causality between physical frailty and sleep disturbances in this population.

Prevalence, overlap, and prognostic impact of multiple frailty domains in older patients on hemodialysis.

BACKGROUND: Frailty is a state of increased vulnerability owing to adverse health outcomes and is recognized as a multidimensional construct. There is limited evidence on the association between multiple domains of frailty and the risk of adverse events in patients undergoing hemodialysis. We aimed to report on the prevalence, degree of overlap, and prognostic impact of multiple frailty domains in older patients undergoing hemodialysis. METHODS: We retrospectively enrolled outpatients (aged ≥60 years) undergoing hemodialysis at two dialysis centers in Japan. The physical domain of frailty was defined as slow gait speed and low handgrip strength. The psychological and social domains of frailty were defined using a questionnaire to assess depressive symptoms and define social frailty status. The outcomes were all-cause mortality, all-cause hospitalization, and cardiovascular hospitalization. Cox proportional hazard and negative binomial models were used to examine these associations. RESULTS: Among the 344 older patients (mean age, 72 years; male, 61%), 15.4% had an overlap in all three domains. Patients with a higher number of frailty domains had a higher risk of all-cause mortality, all-cause hospitalization, and cardiovascular hospitalization (P for trend = 0.001, 0.001, and 0.08, respectively). CONCLUSIONS: These results suggest that multiple-domain assessment of frailty is an important strategy to prevent adverse events in patients requiring hemodialysis.

Effects of anthropometric changes on hospitalization and mortality among patients on hemodialysis.

BACKGROUND: Low values for anthropometric indicators are risk factors for adverse clinical outcomes among patients on hemodialysis. Nonetheless, little is known about the association between the trajectory of anthropometric indicators and prognosis. We examined the association between a one-year change in anthropometric indicators and hospitalization and mortality in patients undergoing hemodialysis. METHODS: This retrospective cohort study collected data on five anthropometric indicators from patients undergoing maintenance hemodialysis: body mass index, mid-upper arm circumference, triceps skinfold, mid-arm muscle circumference, and calf circumference. We calculated their trajectories over one year. The outcomes were all-cause death and the number of all-cause hospitalizations. Negative binomial regressions were used to examine these associations. RESULTS: We included 283 patients (mean age, 67.3 years; 60.4% males). During the follow-up period (median, 2.7 years), 30 deaths and 200 hospitalizations occurred. Body mass index (incident rate ratio [IRR]: 0.87; 95% confidence interval [CI] 0.85-0.90), mid-upper arm circumference (IRR: 0.94; 95% CI 0.88-0.99), triceps skinfold (IRR: 0.92; 95% CI 0.84-0.99), and mid-arm muscle circumference (IRR: 0.99; 95% CI 0.98-0.99) increases over one year were associated with a lower risk of all-cause hospitalizations and death regardless of their value at any one point in time. However, the calf circumference trajectory was not associated with clinical events (IRR: 0.94; 95% CI 0.83-1.07). CONCLUSIONS: Body mass index, mid-upper arm circumference, triceps skinfold, and mid-arm muscle circumference trajectories were independently associated with clinical events. Routinely assessing these simple measures in clinical practice may provide additional prognostic information for managing patients undergoing hemodialysis.

Physical function and physical activity in hemodialysis patients with peripheral artery disease.

INTRODUCTION: Peripheral artery disease (PAD) is commonly observed in patients undergoing hemodialysis. PAD impairs the vasculature and leads to pathophysiologic changes in the skeletal muscles, causing physical function impairment and physical inactivity in general. However, it is unclear whether PAD adversely affects physical function and physical activity in patients on hemodialysis. METHODS: We performed a cross-sectional study with a retrospective review of the data to determine whether PAD is associated with impaired physical function and physical activity in patients undergoing hemodialysis. The study population comprised 310 patients and 88 healthy subjects. PAD was diagnosed based on an ankle-brachial index of <1.00 in patients on hemodialysis. Measurements of physical function included maximum walking speed, muscle strength in the lower extremities, and balance while standing. FINDINGS: Of the 310 patients, 84 (27.1%) had PAD. When patients undergoing hemodialysis were divided into those without PAD and those with PAD, both groups had poorer physical function and physical activity than the healthy control subjects. After adjustments for potential confounders, it was found that patients on hemodialysis with PAD had slower walking speed, poorer standing balance, and less physical activity than those without PAD. However, there was no significant difference in lower extremity muscle strength between the two groups. DISCUSSION: PAD diagnosed based on an ankle-brachial index of <1.00 was independently associated with impaired physical function and reduced physical activity in patients undergoing hemodialysis.

Comparison of the association between six different frailty scales and clinical events in patients on hemodialysis.

BACKGROUND: Frailty is associated with adverse outcomes in patients undergoing hemodialysis (HD). However, no study has used various frailty assessments in patients on HD to examine their association with clinical events. In this study, we investigated the association between clinical events and six frailty scales. METHODS: Outpatients who underwent HD between 2018 and 2020 were retrospectively enrolled. Frailty was defined using the Fried Frailty Phenotype, Study of Osteoporotic Fractures (SOF) Index, Short Physical Performance Battery (SPPB), Frail Screening Index, FRAIL scale and Clinical Frailty Scale. Outcomes were clinical events, including a composite of multiple (i.e. recurrent) all-cause hospitalizations, fractures and/or all-cause mortality. The association of clinical events and the frailty scales were investigated using negative binomial regression analysis. RESULTS: Fried Frailty Phenotype [incident rate ratio (IRR), 1.62; 95% confidence interval (CI), 1.49-1.76], SOF Index (IRR, 1.42; 95% CI, 1.10-1.83), SPPB (IRR, 1.79; 95% CI, 1.11-2.88) and Clinical Frailty Scale (IRR, 1.65; 95% CI, 1.04-2.61) were significantly associated with clinical events. However, Frail Screening Index (IRR, 1.38; 95% CI, 0.60-3.18) and FRAIL scale (IRR, 1.30; 95% CI, 0.88-1.92) showed no significant association with clinical events. CONCLUSIONS: Objective frailty assessments (SPPB) and medical staff impression-based frailty (Clinical Frailty Scale) may be useful prognostic predictors for patients on HD. Questionnaire-based frailty assessment should be carefully considered when used as a measurement of frailty.

Simplified discriminant parameters for sarcopenia among patients undergoing haemodialysis.

BACKGROUND: Patients with end-stage renal disease (ESRD) are at an increased risk of developing sarcopenia, which can lead to various adverse health outcomes. Although the diagnosis of sarcopenia is essential for clinical management, it is not feasible in routine clinical practice for populations undergoing haemodialysis because it is time-consuming and resources are limited. Serum creatinine levels in patients with ESRD have been gaining attention as a screening parameter for sarcopenia because serum creatinine is a routinely measured byproduct of skeletal muscle metabolism. This study aimed to evaluate the discriminative ability of the creatinine-derived index for sarcopenia in patients undergoing haemodialysis. METHODS: We diagnosed sarcopenia according to the Asian Working Group for Sarcopenia (AWGS) 2 criteria in 356 clinically stable outpatients with ESRD enrolled from three dialysis facilities. We adopted the modified creatinine index as a simplified discriminant parameter for sarcopenia in addition to the calf circumference, SARC-F score, and combination of both (i.e. SARC-CalF score), which are recommended by the AWGS. Receiver operating characteristic analysis and logistic regression analysis were conducted to evaluate the discriminative ability of the modified creatinine index for sarcopenia. RESULTS: Of the study participants, 142 (39.9%) were diagnosed with sarcopenia. The areas under the curve of the modified creatinine index against sarcopenia in the male and female participants were 0.77 (95% confidence interval [CI]: 0.71 to 0.83) and 0.77 (95% CI: 0.69 to 0.85), respectively. All simplified discriminant parameters were significantly associated with sarcopenia, even after adjusting for patient characteristics and centre. In the comparison of the odds ratios for sarcopenia for 1-standard deviation change in the simplified discriminant parameters, the odds ratio of the modified creatinine index was 1.92 (95% CI: 1.15 to 3.19), which was lower than that of the calf circumference (odds ratio: 6.58, 95% CI: 3.32 to 13.0) and similar to that of the SARC-F (odds ratio: 1.57, 95% CI: 1.14 to 2.16) and SARC-CalF scores (odds ratio: 2.36, 95% CI: 1.60 to 3.47). CONCLUSIONS: This study revealed a strong association between the creatinine-derived index and sarcopenia in patients undergoing haemodialysis. The modified creatinine index was equal or superior to those of SARC-F and SARC-CalF score in discriminability for sarcopenia. However, the ability of the calf circumference to discriminate sarcopenia is extremely high, and further study is needed to determine whether it can be used to detect deterioration of muscle mass and function over time.

Associations between dynapenia, cardiovascular hospitalizations, and all-cause mortality among patients on haemodialysis.

BACKGROUND: Low muscle strength is associated with adverse clinical outcomes in patients undergoing haemodialysis (HD). No studies have reported the association between dynapenia, defined by both low handgrip strength (HGS) and quadriceps isometric strength (QIS), and long-term clinical outcomes in patients on HD. We examined the associations between dynapenia, cardiovascular (CV) hospitalizations, and all-cause mortality in the HD population. METHODS: This retrospective study used data from outpatients undergoing HD at two dialysis facilities between October 2002 and March 2020. We defined low muscle strength as an HGS of <28 kg for men and <18 kg for women and a QIS of <40% dry weight. Furthermore, we categorized dynapenia into three groups: robust ('high HGS and high QIS'), either low HGS or low QIS ('low HGS only' or 'low QIS only'), and dynapenia ('low HGS and low QIS'). The outcomes were all-cause mortality and a composite of CV hospitalizations and mortality. Cox proportional hazards and negative binomial models were used to examine these associations. RESULTS: A total of 616 patients (mean age, 65.4 ± 12.2 years; men, 61%) were included in the analyses. During the follow-up (median, 3.0 years), a total of 163 deaths and 288 CV hospitalizations occurred. Patients with the either low HGS or low QIS [hazard ratio (HR), 1.75; 95% confidence intervals (CIs), 1.46-2.10] and dynapenia (HR, 2.80; 95% CIs, 2.49-3.14) had a higher risk of mortality than those in the robust group. When compared with the robust group, the either low HGS or low QIS [incidence rate ratio (IRR): 1.41, 95% CI: 1.00-1.99] and dynapenia (IRR: 2.04, 95% CI: 1.44-2.89) groups were associated with a significantly higher incident risk of CV hospitalizations. CONCLUSIONS: Dynapenia (muscle weakness in both upper and lower extremities) was associated with increased risks of all-cause mortality and CV hospitalizations among patients on HD. Screening for dynapenia using both HGS and QIS may be useful for prognostic stratification in the HD population.

Feasibility of long-term intradialytic exercise for older patients receiving hemodialysis: a retrospective single-center study.

PURPOSE: Decreased physical function and physical activity are associated with adverse outcomes among patients undergoing hemodialysis (HD). Although intradialytic exercise (IDEx) can help improve physical function, few studies have evaluated whether long-term IDEx could improve physical function or physical activity in older HD patients. This study aimed to investigate the effects of intradialytic exercise (IDEx) on physical function and physical activity in older HD patients over a 24-month period. METHODS: This retrospective study included clinically stable Japanese HD patients (aged ≥ 60 years) who visited our outpatient clinic. The patients were categorized into the IDEx (underwent IDEx) and non-IDEx (did not undergo IDEx) groups. The IDEx group underwent a 30-40 min low-intensity resistance training for three times/week during the HD period. Baseline, 12-month, and 24-month follow-up assessments were conducted to assess patient characteristics, physical function, and physical activity. Results were compared using generalized estimating equations. RESULTS: The study included 57 patients with complete follow-up data. Baseline, 12-month, and 24-month follow-up assessments revealed no significant inter-group differences concerning physical function, physical activity, and other measurements. CONCLUSION: IDEx was shown to have limited effect on physical function and physical activity among older HD patients in a clinical setting. Future studies are needed to re-evaluate IDEx programs in HD patients by incorporating exercises performed before and after the HD session.

Modified Creatinine Index and Clinical Outcomes of Hemodialysis Patients: An Indicator of Sarcopenia?

OBJECTIVE: Sarcopenia (especially muscle mass assessed using gold standard techniques) has been suggested as a poorer predictor of mortality than muscle function in patients undergoing hemodialysis. Appropriate methods to estimate muscle mass for use as a good predictor of clinical outcomes remain to be established. We investigated whether the modified creatinine index (mCI), which is a surrogate marker of muscle mass, could predict mortality and cardiovascular (CV) hospitalizations independent of muscle function and other confounders in patients on hemodialysis. DESIGN AND METHODS: In this retrospective study, outpatients (n = 542; mean age, 65.3 years; 60% men; median dialysis vintage, 29 months; mean BMI, 22.0 kg/m2) undergoing hemodialysis were investigated. The mCI, handgrip strength, and gait speed were assessed and related to all-cause mortality and a composite of CV hospitalizations and all-cause mortality. Cox proportional and mixed-effects negative binomial models were fit for mortality and the composite outcomes. RESULTS: Patients were followed up for a median 3 years (interquartile range: 1.5-5.7). Each per SD increase of mCI (HR:0.63, 95% CI:0.62-0.65), handgrip strength (HR:0.51, 95% CI:0.48-0.54), and gait speed (HR:0.60, 95% CI:0.56-0.64) were significantly associated with lower all-cause mortality rates after adjusting for covariates. The mCI was consistently found to be an independent predictor of mortality after additional adjustment for handgrip strength or gait speed. Furthermore, sarcopenic conditions [i.e., lower mCI, and lower handgrip strength (HR:3.79, 95% CI:2.09-6.87) or slower gait speed (HR:4.20, 95% CI:2.38-7.41)] were significantly associated with a higher risk of mortality after adjusting for covariates. Associations of mCI with multiple CV hospitalizations and mortality were similar to those between mCI and mortality. CONCLUSION: The mCI was a good predictor of clinical outcomes and was comparable to muscle function, including handgrip strength and gait speed. The mCI is likely to provide additional diagnostic and prognostic values for sarcopenia in patients on hemodialysis.

Impact of Physical Activity on Dialysis and Nondialysis Days and Clinical Outcomes Among Patients on Hemodialysis.

OBJECTIVE: Patients undergoing hemodialysis (HD) have different physical activity (PA) patterns on HD and non-HD days. Nonetheless, whether these differences are associated with clinical outcomes remains unclear. We examined the association of PA levels on HD and non-HD days with cardiovascular (CV) hospitalizations and mortality. METHODS: Outpatients undergoing HD from 2002 to 2019 were retrospectively enrolled. The number of steps performed over 3 HD days and 4 non-HD days was recorded via accelerometry. Outcomes were all-cause mortality and a composite of CV hospitalizations and mortality. Patients were divided into two groups, each according to the median number of steps performed on HD (2371 steps/day) and non-HD days (3752 steps/day). Further, we categorized them into 4 groups according to each median values: "more active on HD/more active on non-HD (MM)," "more active on HD/less active on non-HD (ML)," "less active on HD/more active on non-HD (LM)," and "less active on HD/less active on non-HD (LL)." Cox and mixed-effects Poisson regression models were used for these outcomes. RESULTS: We analyzed 512 patients (median follow-up, 3.4 years). Higher PA on HD (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.54-0.65), and non-HD (HR, 0.84; 95% CI, 0.80-0.88) was associated with lower mortality risk, respectively. Further, the ML group (HR, 1.20; 95% CI, 1.13-1.28), LM group (HR, 1.82; 95% CI, 1.53-2.17), and LL group (HR, 1.83; 95% CI, 1.65-2.02) had higher mortality risks than the MM group. Associations of PA with multiple CV hospitalizations and mortality were similar to those between PA and mortality. CONCLUSIONS: Higher PA on HD and non-HD days was associated with lower risks of CV hospitalizations and mortality. However, higher PA levels on either HD or non-HD days alone did not improve clinical outcomes.

Alterations in proteoglycan components and histopathology of the peritoneum in uraemic and peritoneal dialysis (PD) patients.

BACKGROUND: Proteoglycans (PGs) are dominant extracellular matrices (ECMs) in the peritoneal tissues. Human peritoneal mesothelial cells synthesize small proteoglycans including decorin. Peritonitis and long-term peritoneal dialysis (PD) cause fibrotic changes in the peritoneum that result in ECM remodelling and PG synthesis. METHODS: Twenty-five peritoneal tissues from eight patients at initiation of PD, five long-term PD (>6 years) patients with severe peritonitis lasting for almost 1 month, nine patients after long-term PD (>6 years) without peritonitis and three normal subjects were included in the present study. Expressions of decorin, versican, hyaluronan, MMP-2, alfa smooth muscle actin (alphaSMA) and CD68 for macrophages in these specimens were examined by immunohistochemical staining. RESULTS: Although expression of decorin was detected in normal subjects, it was markedly decreased with long-term PD treatment. In long-term PD patients, the expression of versican was observed in their fibrotic-thickened peritoneum. Versican was present in fibrous regions, elastic lamina of the peritoneum, vascular walls and perivascular regions. Hyaluronan was observed in the whole thickened peritoneum, but its distribution differed in part from that of versican. MMP-2 was mainly observed around the blood vessels. Alfa SMA-positive cells, namely 'myofibroblasts' and CD68-positive cells, i.e. macrophages, were observed in the fibrotic-thickened peritoneum of long-term PD patients. Expressions of MMP-2, hyaluronan, SMA and CD68 in the peritoneum were marked in long-term PD patients' samples, which were strongly immunostained by versican, and were especially high in peritonitis patients. CONCLUSIONS: It appears that alterations in PGs, including marked induction of versican with peritonitis and disappearance of decorin, are involved in peritoneal remodelling in PD patients. Versican expression was closely related to the appearance of myofibroblasts and macrophages. These observations suggest that the alteration in PG components following PD therapy and severe inflammation contribute to fibrous thickening of the peritoneum.

Effect of pitavastatin on urinary liver-type fatty acid-binding protein levels in patients with early diabetic nephropathy.

OBJECTIVE: Liver-type fatty acid-binding protein (l-FABP) is expressed in renal proximal tubules and is reported to be a useful marker for progression of chronic glomerulonephritis. The aim of this study was to determine whether urinary l-FABP levels are altered at various stages of diabetic nephropathy and whether pitavastatin affects urinary l-FABP levels in early diabetic nephropathy. RESEARCH DESIGN AND METHODS: Fifty-eight patients with type 2 diabetes (34 men and 24 women, median age 52 years) and 20 healthy, age-matched subjects (group E) were recruited for the study. The diabetic patients included 12 patients without nephropathy (group A), 20 patients with microalbuminuria (group B), 14 patients with macroalbuminuria and normal renal function (group C), and 12 patients with chronic renal failure but not undergoing hemodialysis (blood creatinine >1.2 mg/dl; mean 2.5 mg/dl, group D). Twenty group B patients were randomly assigned to receive 1 mg/day pitavastatin (10 patients, group B1) or placebo (10 patients, group B2). Treatment was continued for 12 months. Urinary l-FABP levels were measured by enzyme-linked immunosorbent assay. Urinary 8-hydroxydeoxyguanosine and serum free fatty acids (FFAs) were also measured in group B. RESULTS: Urinary l-FABP levels in groups A-D were 6.2 +/- 4.6 microg/g creatinine, 19.6 +/- 13.5 microg/g creatinine, 26.8 +/- 20.4 microg/g creatinine, and 52.4 +/- 46.8 microg/g creatinine, respectively. Urinary l-FABP levels in groups B-D were significantly higher than those in healthy subjects (group E, 5.8 +/- 4.0 microg/g creatinine) (group B, P < 0.05; group C, P < 0.01; group D, P < 0.01). In group B1, urinary albumin excretion (UAE) and urinary l-FABP levels were decreased after pitavastatin treatment (UAE before, 110 +/- 74 microg/min; 6 months, 88 +/- 60 microg/min, P < 0.05; 12 months, 58 +/- 32 microg/min, P < 0.01; l-FABP before, 18.6 +/- 12.5 microg/g creatinine; 6 months, 12.2 +/- 8.8 microg/g creatinine, P < 0.05; 12 months, 8.8 +/- 6.4 microg/g creatinine, P < 0.01). In group B2, UAE and l-FABP levels showed little change during the experimental period. In group B1, urinary 8-hydroxydeoxyguanosine was decreased 12 months after pitavastatin treatment (before 32.5 +/- 19.5 ng/mg creatinine, after 18.8 +/- 14.5 ng/mg creatinine, P < 0.01), but in group B2, these showed little difference during the experimental period. In both groups B1 and B2, serum FFAs showed little difference during the experimental period. CONCLUSIONS: Urinary l-FABP levels appear to be associated with the progression of diabetic nephropathy, and pitavastatin may be effective in ameliorating tubulointerstitial damage in early diabetic nephropathy.

Candesartan reduces urinary fatty acid-binding protein excretion in patients with autosomal dominant polycystic kidney disease.

BACKGROUND: Free fatty acids (FFAs) bound to albumin are overloaded in renal proximal tubules and exacerbate tubulointerstitial damage. Liver-type fatty acid-binding protein (L-FABP) is an intracellular carrier protein of FFAs that is expressed in renal proximal tubules in humans. Urinary L-FABP reflects the clinical prognosis of chronic glomerulonephritis. The aim of the present study was to determine whether urinary L-FABP excretion is altered in patients with autosomal dominant polycystic kidney disease (ADPKD) and whether candesartan cilexetil, an angiotensin II receptor antagonist, affects these levels. METHODS: Subjects comprised 20 normotensive ADPKD patients (8 men and 12 women, mean age 42.6 years) and 20 age-matched healthy volunteers (8 men and 12 women, mean age 44.0 years). The 20 ADPKD patients participated in a randomized double-blind placebo-controlled study of candesartan cilexetil for 6 months. Urinary L-FABP levels were measured by a newly established ELISA method. RESULTS: Urinary L-FABP levels were significantly higher in ADPKD patients (154.5 +/- 110.6 microg/g Cr) than in healthy subjects (5.5 +/- 3.8 microg/g Cr) (P < 0.001). Candesartan cilexetil reduced urinary L-FABP levels from 168.5 +/- 104.5 microg/g Cr to 98.5 +/- 68.5 microg/g Cr after 3 months (P < 0.01) and to 44.6 +/- 30.8 microg/g Cr after 6 months (P < 0.001). Placebo had no effect on L-FABP levels (before, 140.5 +/- 100.5 microg/g Cr; at 3 months, 148.5 +/- 108.5 microg/g Cr; at 6 months, 150.5 +/- 110.8 microg/g Cr). During the 6 months, serum creatinine, blood urea nitrogen, 24-hour creatinine clearance and blood pressure showed little change in either group. CONCLUSIONS: Increased urinary L-FABP levels may be associated with the development of ADPKD, and candesartan cilexetil has a beneficial effect on reducing these levels.

Hemoperfusion with polymyxin B-immobilized fiber in septic patients with methicillin-resistant Staphylococcus aureus-associated glomerulonephritis.

BACKGROUND/AIMS: We investigated whether urinary podocytes are present in septic patients with methicillin-resistant Staphylococcus aureus (MRSA)-associated glomerulonephritis and whether polymyxin B-immobilized fiber (PMX-F) treatment affects proteinuria and urinary podocyte excretion in these patients. METHODS: Twenty septic patients with MRSA-associated glomerulonephritis (mean age: 63.7 years) and 80 septic patients whose MRSA infection was not followed by glomerulonephritis (mean age: 60.5 years) were included in this study. All septic patients were treated with fosfomycin sodium, beta-lactams, arbekacin sulfate, and teicoplanin, or a combination of these. Twenty septic patients with MRSA-associated glomerulonephritis were randomly assigned to one of two treatments: PMX-F treatment (group A, n = 10) and conventional treatment (group B, n = 10). PMX-F treatment was repeated twice. RESULTS: Urinary podocytes and urinary protein excretion were not detected in MRSA septic patients without glomerulonephritis. However, urinary podocytes (1.7 +/- 0.6 cells/ml) and proteinuria (2.6 +/- 0.6 g/d) were detected in the 20 septic patients with MRSA-associated glomerulonephritis. Plasma endotoxin levels were decreased from 13.6 +/- 4.6 pg/ml to 6.6 +/- 2.2 pg/ml (p < 0.05) in group A. Levels in group B, however, showed little difference after treatment. Urinary podocytes were reduced in group A (from 1.8 +/- 0.6 cells/ml to 0.4 +/- 0.2 cells/ml, p < 0.01) as was urinary protein excretion (from 3.0 +/- 0.5 g/d to 0.8 +/- 0.4 g/d, p < 0.01) but urinary podocytes and protein excretion levels showed little difference after treatment in group B. CONCLUSION: PMX-F treatment may be effective in reducing urinary protein and urinary podocyte excretion in septic patients with MRSA-associated glomerulonephritis.

Evaluation of parathyroid hyperplasia by ultrasonographic examination in patients with end-stage renal failure before and at initiation of dialysis.

Secondary hyperparathyroidism (2HPT), which is related to renal osteodystrophy (ROD), may occur in patients in the comparatively early stage of chronic renal failure (CRF). Secondary hyperparathyroidism patients with parathyroid hyperplasia showed resistance to vitamin D(3) treatment during long-term dialysis. At present, evaluation by ultrasonography is considered to be useful for confirming parathyroid hyperplasia. There are no clinical data associated with imaging evaluation of 2HPT in CRF patients. In the present study, the relationship among clinical and biochemical data, and parathyroid hyperplasia by ultrasonography, was evaluated in 12 patients (six males and six females) with end-stage renal failure (ESRF) before and at initiation of dialysis. Five patients showed an enlargement of parathyroid glands in ultrasonography. Levels of serum-intact parathyroid hormone (PTH) in patients with parathyroid hyperplasia (positive group) were significantly higher than in those without hyperplasia (negative group; 97.6 +/- 36.65 vs 17.4 +/- 4.45 pmol/L; P < 0.05). The levels of intact PTH were above 35.0 pmol/L in all five patients with hyperplasia. All patients in the positive group had never taken vitamin D(3) supplements. Calcium-containing phosphate binders were not prescribed before the present study, except in one patient. Parathyroid hyperplasia caused by 2HPT was recognized in patients before and at initiation of dialysis in this study. It appears that untreated 2HPT in CRF patients may progress to advanced 2HPT in ESRF before and/or after the early stage of dialysis. The levels of serum intact PTH are useful in predicting parathyroid hyperplasia.

Effect of cerivastatin on proteinuria and urinary podocytes in patients with chronic glomerulonephritis.

BACKGROUND: We previously reported urinary podocytes to be a marker of glomerular injury. The aim of the present study was to determine whether cerivastatin, a newly developed, potent synthetic statin, affects proteinuria and urinary podocyte excretion in patients with chronic glomerulonephritis (CGN). METHODS: We randomly assigned 40 normotensive hypercholesterolemic patients with CGN to receive either cerivastatin 0.15 mg/day (n=20) or placebo (n=20). Subjects comprised 24 men and 16 women, with a mean age of 40.8+/-14.4 years; 27 had IgA nephropathy and 13 had non-IgA proliferative glomerulonephritis. Treatment was continued for 6 months. Plasma total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides, urinary protein excretion and the number of podocytes were measured before treatment and at 3 and 6 months after treatment. RESULTS: After 6 months, a significant reduction in total cholesterol (P<0.001), LDL-cholesterol (P<0.001) and triglycerides (P<0.05), and a significant increase in HDL-cholesterol (P<0.001) were observed in the group treated with cerivastatin. Urinary protein excretion decreased from 1.8+/-0.6 to 0.8+/-0.4 g/day, (P<0.01) in this group, and urinary podocyte excretion decreased from 1.6+/-0.6 to 0.9+/-0.4 cells/ml (P<0.01). However, placebo showed little effect on these lipid levels, urinary protein excretion and urinary podocyte excretion. The differences between the cerivastatin group and the placebo group were significant (cholesterol, P<0.001; LDL-cholesterol, P<0.001; triglycerides, P<0.05; HDL-cholesterol, P<0.001; urinary protein, P<0.01; and urinary podocytes, P<0.01). CONCLUSION: Statins such as cerivastatin may be beneficial for restoration of injured podocytes in patients with CGN and hypercholesterolaemia.

Effect of dilazep dihydrochloride on serum cardiac troponin T levels in hemodialysis patients.

BACKGROUND/AIM: Cardiac troponin T is a highly sensitive marker for the detection of myocardial injury. We studied whether dilazep dihydrochloride affects cardiac troponin T levels in hemodialysis patients. METHODS: Our study included 60 hemodialysis patients without symptoms of acute myocardial ischemia. We measured serum cardiac troponin T levels by the Elecsys troponin T assay and randomized 40 hemodialysis patients with left ventricular hypertrophy (LVH) into two treatment groups: a dilazep dihydrochloride group (300 mg/day, n = 20) and a placebo group (n = 20). Treatment was continued for 12 months. RESULTS: There were no significant differences between pre- and postdialysis cardiac troponin T levels before treatment. LVH was noted in 40 patients out of 60 hemodialysis patients (67%). Cardiac troponin T levels were significantly higher in these patients (0.23 +/- 0.08 microg/l) than in hemodialysis patients without LVH (0.09 +/- 0.03 microg/l). Cardiac troponin T levels were reduced from 0.24 +/- 0.08 to 0.12 +/- 0.06 microg/l (p < 0.01) in patients treated with dilazep dihydrochloride. There were no change in cardiac troponin T levels in patients receiving placebo (from 0.21 +/- 0.08 at baseline to 0.20 +/- 0.07 microg/l). CONCLUSION: Dilazep dihydrochloride may be effective in ameliorating myocardial damage in hemodialysis patients.