Body fluid volume calculated using the uric acid kinetic model relates to the vascular event.

PURPOSE: We developed a method to measure the extracellular and intracellular fluid volumes using the kinetics of uric acid in the bodies of Japanese patients undergoing dialysis. In this research, we aimed to assess the prognosis of vascular events using this uric acid kinetic model method. METHODS: We conducted a retrospective cohort study of 1,298 patients who were undergoing hemodialysis or predilution online hemodiafiltration at the end of December 2019 at 13 institutions in Japan. Information on vascular events was acquired in 2020. Vascular event prognosis was defined as the new incidence of one or more of the following four types of vascular events: myocardial infarction, cerebral infarction, cerebral hemorrhage, or limb amputation. We measured the extracellular fluid volume and intracellular fluid volume after dialysis using the uric acid kinetic model method and determined the association between ECV, ICV, and vascular event risk. RESULTS: A high extracellular volume was substantially linked to an increased risk of vascular events. In addition, while a crude analysis revealed that a high intracellular volume was associated with a low risk of vascular events, this was not statistically significant after multifactorial adjustment. This result was partly affected by the low measurement accuracy of the serum urea nitrogen level used for the intracellular volume calculation. CONCLUSIONS: Extracellular volume calculated using the uric acid kinetic model method is a prognostic factor for vascular events in patients undergoing hemodialysis.

Associations between N-Terminal Pro-B-Type Natriuretic Peptide, Body Fluid Imbalance and Quality of Life in Patients Undergoing Hemodialysis: A Cross-Sectional Study.

Natriuretic peptides may be associated with the complex interaction between malnutrition and fluid overload. This study assessed the relationship between N-terminal pro-B-type natriuretic peptide (NT-proBNP), body fluid composition, and quality of life (QOL) domains. A multicenter, cross-sectional study was conducted between 2019 and 2022. The QOL survey of 322 patients undergoing maintenance hemodialysis (227 men and 95 women; mean age, 65 ± 12 years) was conducted using the Kidney Disease QOL-Short Form v. 1.3. The patients in the higher NT-proBNP quartile group were older and had a longer dialysis vintage; lower body mass index, serum albumin, blood urea nitrogen, creatinine, sodium, uric acid, total cholesterol, triglycerides, and hemoglobin levels; lower geriatric nutritional risk index (GNRI), skeretal mascle mass index, and phase angle (PhA); and higher pre- and post-dialysis systolic blood pressure (BP), cardiothoracic index, and C-reactive protein (CRP) (p < 0.05). Multivariate analysis revealed that post-dialysis systolic BP, CRP, and GNRI or PhA were independently associated with NT-proBNP. The higher NT-proBNP group experienced muscle attenuation and/or inflammation and an enlarged left atrium. Consequently, the elevated NT-proBNP by such an imbalance in body fluid composition is associated with lower health-related QOL.

Vesicoureteral Reflux Causes Interstitial Inflammation in Pediatric Kidney Allograft: A Clinicopathological Analysis of 1-Year Protocol Biopsies.

INTRODUCTION: At present, there is limited evidence of the histological impact of vesicoureteral reflux (VUR) on pediatric kidney allografts. In this study, we aimed to investigate the relationship between VUR diagnosed by voiding cystourethrography (VCUG) and 1-year protocol biopsy results. METHODS: One hundred thirty-eight pediatric kidney transplantations were performed in Toho University Omori Medical Center between 2009 and 2019. We included 87 pediatric transplant recipients who were evaluated for VUR by VCUG prior to or at the time of the 1-year protocol biopsy and underwent a 1-year protocol biopsy after transplantation. We evaluated the clinicopathological findings of the VUR and non-VUR groups, and histological scores were evaluated using the Banff score. Tamm-Horsfall protein (THP) within the interstitium was identified by light microscopy. RESULTS: Of the 87 transplant recipients, 18 cases (20.7%) were diagnosed with VUR by VCUG. The clinical background and findings were not significantly different between the VUR and non-VUR groups. The pathological findings revealed a significantly higher Banff total interstitial inflammation (ti) score in the VUR group than in the non-VUR group. Multivariate analysis indicated a significant relationship between the Banff ti score and THP within the interstitium, and VUR. The 3-year protocol biopsy results (n = 68) revealed a significantly higher Banff interstitial fibrosis (ci) score in the VUR group than in the non-VUR group. CONCLUSION: VUR caused interstitial fibrosis in the 1-year pediatric protocol biopsies, and interstitial inflammation at the 1-year protocol biopsy may affect interstitial fibrosis at the 3-year protocol biopsy.

Association between Intra- and Extra-Cellular Water Ratio Imbalance and Natriuretic Peptides in Patients Undergoing Hemodialysis.

Natriuretic peptides are associated with malnutrition and volume overload. Over-hydration cannot simply be explained by excess extracellular water in patients undergoing hemodialysis. We assessed the relationship between the extracellular and intracellular water (ECW/ICW) ratio, N-terminal pro-B-type natriuretic peptide (NT-proBNP), human atrial natriuretic peptide (hANP), and echocardiographic findings. Body composition was examined by segmental multi-frequency bioelectrical impedance analysis in 368 patients undergoing maintenance dialysis (261 men and 107 women; mean age, 65 ± 12 years). Patients with higher ECW/ICW ratio quartiles tended to be older, were on dialysis longer, and had higher post-dialysis blood pressure and lower body mass index, ultrafiltration volume, serum albumin, blood urea nitrogen, and creatinine levels (p < 0.05). The ECW/ICW ratio significantly increased with decreasing ICW, but not with ECW. Patients with a higher ECW/ICW ratio and lower percent fat had significantly higher natriuretic peptide levels. After adjusting for covariates, the ECW/ICW ratio remained an independent associated factor for natriuretic peptides (ß = 0.34, p < 0.001 for NT-proBNP and ß = 0.40, p < 0.001 for hANP) and the left ventricular mass index (ß = 0.20, p = 0.002). The ICW-ECW volume imbalance regulated by decreased cell mass may explain the reserve capacity for fluid accumulation in patients undergoing hemodialysis.

Quantitative sonographic assessment of quadriceps muscle thickness for fall injury prediction in patients undergoing maintenance hemodialysis: an observational cohort study.

BACKGROUND: Accidental fall risk is high in patients undergoing maintenance hemodialysis. Falls are associated with fatal injury, comorbidities, and mortality. Risk assessment should be a primary component of fall prevention. This study investigated whether quadriceps muscle thickness measured using ultrasonography can predict fall injury among dialysis patients. METHODS: Using an observational cohort study design, 180 ambulatory hemodialysis patients were recruited from 2015 to 2016 from four dialysis clinics. The sum of the maximum quadriceps muscle thickness on both sides and the average of the maximum thigh circumference and handgrip strength after hemodialysis were calculated. Patients were stratified according to tertiles of quadriceps muscle thickness. Fall injury was surveyed according to the patient's self-report during the one-year period. RESULTS: Among the 180 hemodialysis patients, 44 (24.4%) had fall injuries during the 12-month follow-up period. When the quadriceps muscle thickness levels were stratified into sex-specific tertiles, patients in the lowest tertile were more likely to have a higher incidence of fall injury than those in the higher two tertiles (0.52 vs. 0.19 and 0.17 fall injuries/person-year). After adjusting for covariates, lower quadriceps muscle thickness was found to be an independent predictor of fall injury (hazard ratio [95% confidence interval], 2.33 [1.22-4.52], P < 0.05). Receiver operating characteristic curves were constructed to determine the optimal cutoffs of quadriceps muscle thickness, thigh circumference, and handgrip strength that best predicted fall injury (quadriceps muscle thickness, 3.37 cm and 3.54 cm in men and women; thigh circumference, 44.6 cm and 37.2 cm in men and women; and handgrip strength, 23.3 kg and 16.5 kg in men and women). Using these cutoff values, the areas under the curve were 0.662 (95% CI, 0.576-0.738), 0.625 (95% CI, 0.545-0.699), and 0.701 (95% CI, 0.617-0.774), for quadriceps muscle thickness, thigh circumference, and handgrip strength, respectively. Quadriceps muscle thickness was a more precise predictor of fall injury than thigh circumference and had similar diagnostic performance as handgrip strength tests in dialysis patients. CONCLUSIONS: Quadriceps muscle thickness can be measured easily at the bedside using ultrasonography and is a precise predictor of fall injury in patients undergoing maintenance hemodialysis.

Prevalence of hypothyroidism in Japanese chronic kidney disease patients.

Background: Major symptoms of progressive chronic kidney disease (CKD) are similar to those of hypothyroidism. Hidden symptoms of hypothyroidism underlying CKD are often observed in clinical practice. This study aimed to ascertain the frequency of hypothyroidism complicated by CKD, and to analyze factors impacting thyroid function.Methods: During the period from April 2012 through October 2016, 510 CKD patients at our outpatient clinic were measured thyroid and kidney function for diagnosing hypothyroidism (overt hypothyroidism, OH; subclinical hypothyroidism, SH; non-thyroidal illness, NTI) and evaluating the stage of CKD. All patients were over 15 years of age.Results: There were significant differences in age, estimated glomerular filtration rate (eGFR), urinary protein (UP), and serum albumin (Alb) among patients with OH, SH, and NTI compared to the normal group in univariate and multivariate analyses. UP showed the highest odds ratio of OH, SH, and NTI but no differences were recognized in gender in each group. Frequency distribution showed that the prevalence of thyroid dysfunction was greater among more severe stage of CKD with higher amount of UP. OH and SH did not show high positive ratio of anti-thyroglobulin antibody (TgAb) and anti-thyroid peroxidase antibody (TPOAb). NTI and normal subjects showed higher positive ratio as 50.0% and 42.9% of TgAb and TPOAb than OH and SH.Conclusions: Hypothyroidism complicated by CKD exhibited a high prevalence. Age, eGFR, UP, and serum Alb were related to the prevalence of hypothyroidism, whereas gender was not and this was contradicted to the prevalence of hypothyroidism in general population. The prevalence of OH and SH was higher among patients with higher stage of CKD with increased UP. Hypothyroidism complicated by CKD may involve different onset mechanisms unrelated to antithyroid antibodies (ATAb). In CKD patients, assessments of OH and SH, as well as NTI, are needed for proper diagnosis.

ABO-incompatible pediatric kidney transplantation without antibody removal.

BACKGROUND: Because of the severe shortage of suitable deceased donors, ABO-incompatible living donor kidney transplantation (ABOi LDKT) is performed even in pediatric recipients in Japan. We performed pediatric ABOi LDKT using rituximab without anti-A/B antibody removal. METHODS: Thirteen pediatric recipients (mean age 7.4, range 3.4-15.7, four females) whose baseline anti-A/B IgG titers were ≤ × 64 underwent ABOi LDKT without antibody removal and splenectomy between July 2013 and April 2017 at Toho University. Mycophenolate mofetil (MMF) was initiated on day - 10. Rituximab (100 mg) was administered twice. Basiliximab and triple maintenance immunosuppression (calcineurin inhibitor, MMF, and steroids) were administered. Protocol biopsy was performed at 3 months and 1 year after transplantation. We retrospectively compared the clinical outcomes between these recipients and 37 children (mean age 9.0, range 2.6-18.9, 15 female) who underwent ABO-compatible (ABOc) LDKT during the same period. RESULTS: The mean follow-up periods of ABOi and ABOc groups were 31.9 ± 13.5 and 28.8 ± 14.4 months, respectively. In the ABOi group, no clinical acute rejection (AR) was noted and subclinical AR was observed in four patients without evidence of acute antibody-mediated rejection. In the ABOc group, clinical and subclinical AR developed in 3 and 10 patients, respectively. No significant difference was identified for the mean eGFR between the ABOi and ABOc groups (98.3 ± 48.8 vs. 86.9 ± 39.4, P = 0.452 at 3 months; 78.2 ± 21.2 vs. 79.7 ± 21.3, at 1 year, P = 0.830). Death-censored graft survival at follow-up was 100% in the ABOi group and 94.6% in the ABOc group. Patient survival during the follow-up period in both the groups was 100%. Late-onset neutropenia (LON) requiring granulocyte colony-stimulating factor occurred more frequently in the ABOi group than in the ABOc group (4 vs. 0 patients) (P < 0.001). CONCLUSIONS: Pre- and post-transplantation antibody removal is not a prerequisite for successful pediatric ABOi LDKT, at least in patients with a low anti-A/B IgG antibody titer. However, LON caused by rituximab should be monitored.

Donor-Recipient Body Weight Mismatch May Affect Glomerular Basement Membrane Thinning in Electron Microscopic Examination of 1-Hour Renal Allograft Biopsy Specimens.

BACKGROUND: Although an association between body weight mismatch and impaired graft function has been reported, few histologic studies have evaluated this issue, especially using electric microscopic analysis. During routine observations, we have noted a thin glomerular basement membrane (GBM) in the 1-hour biopsy specimen in cases with an overweight recipient and a lightweight donor. Therefore, we hypothesized that donor-recipient body weight mismatch affects the GBM thickness in the 1-hour biopsy specimen. The aim of the present study was to clarify the effect of donor-recipient body weight mismatch on the GBM thickness of the 1-hour biopsy specimen measured using electron microscopy. METHODS: We used an electron microscope to measure the GBM thickness of specimens at 1-hour post-transplantation (n = 24) and at 1 year post-transplantation (n = 17). The GBM thickness of cases with donor-recipient body weight mismatch was compared with those without mismatch. In accordance with a previous study, we defined a donor/recipient body weight ratio of less than 0.9 as donor-recipient body weight mismatch and a ratio of more than 0.9 as no mismatch. RESULTS: At 1-hour post-transplantation, the mean GBM was significantly thinner in the mismatch group than in the nonmismatch group. However, at 1-year post-transplantation, the mean GBM thickness did not significantly differ between the 2 groups. CONCLUSIONS: The GBM thickness at 1-hour post-transplantation is thinner in cases with donor-recipient body weight mismatch than in cases without mismatch. This implies that donor-recipient body weight mismatch may have to be considered when assessing donor-derived thin GBM disease using the 1-hour biopsy specimen.

Can Lipofuscin Deposition on Renal Allograft Tubular Epithelium Be a Surrogate Marker for Kidney Allograft Aging?

BACKGROUND: Lipofuscin is an indicator of aging. We examined the clinicopathologic significance of lipofuscin deposition in the renal tubules of renal allografts. METHOD: We analyzed allograft biopsy specimens from living kidney transplantations from January to December 2015. For controls, we analyzed native kidney biopsy specimens obtained from January 2015 to December 2016. We identified granules with a yellow-to-tan shade in renal tubules as lipofuscin. RESULTS: The donor age at transplantation was significantly older in lipofuscin deposition biopsy specimens than in those without, whereas the time after transplantation age was not different between the 2 groups with renal allografts. In native kidney biopsies, age at biopsy was significantly older in lipofuscin deposition biopsy specimens than in those without. We compared "massive lipofuscin deposition," defined as lipofuscin deposition on both sides of 3 or more renal tubules, and donor-age matched control allograft biopsies without lipofuscin deposition. Comparing these 2 groups, recipient age at transplantation was significantly older in the massive lipofuscin deposition group. CONCLUSION: Lipofuscin deposition on tubular epithelium is not a surrogate marker of aging of kidneys allografts, although lipofuscin deposition was significantly greater in older tissues from native kidneys. The older age of recipients may be associated with massive lipofuscin deposition in renal allografts.

Diagnostic Performance of Blood Pressure Measurement Modalities in Living Kidney Donor Candidates.

BACKGROUND AND OBJECTIVES: Precise BP measurement to exclude hypertension is critical in evaluating potential living kidney donors. Ambulatory BP monitoring is considered the gold standard method for diagnosing hypertension, but it is cumbersome to perform. We sought to determine whether lower BP cutoffs using office and automated BP would reduce the rate of missed hypertension in potential living donors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We measured BP in 578 prospective donors using three modalities: (1) single office BP, (2) office automated BP (average of five consecutive automated readings separated by 1 minute), and (3) ambulatory BP. Daytime ambulatory BP was considered the gold standard for diagnosing hypertension. We assessed both the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) and the American College of Cardiology/American Heart Association (ACC/AHA) definitions of hypertension in the cohort. Empirical thresholds of office BP and automated BP for the detection of ambulatory BP-diagnosed hypertension were derived using Youden index, which maximizes the sum of sensitivity and specificity and gives equal weight to false positive and false negative values. RESULTS: Hypertension was diagnosed in 90 (16%) prospective donors by JNC-7 criteria and 198 (34%) prospective donors by ACC/AHA criteria. Masked hypertension was found in 3% of the total cohort by JNC-7 using the combination of office or automated BP, and it was seen in 24% by ACC/AHA guidelines. Using Youden index, cutoffs were derived for both office and automated BP using JNC-7 (<123/82 and <120/78 mm Hg) and ACC/AHA (<119/79 and <116/76 mm Hg) definitions. Using these lower cutoffs, the sensitivity for detecting hypertension improved from 79% to 87% for JNC-7 and from 32% to 87% by ACC/AHA definition, with negative predictive values of 95% and 87%, respectively. Missed (masked) hypertension was reduced to 2% and 4% of the entire cohort by JNC-7and ACC/AHA, respectively. CONCLUSIONS: The prevalence of hypertension was higher in living donor candidates using ACC/AHA compared JNC-7 definitions. Lower BP cutoffs in the clinic improved sensitivity and led to a low overall prevalence of missed hypertension in prospective living kidney donors.

Vasa recta hyalinosis reflects severe arteriolopathy in renal allografts.

AIM: We examined the clinicopathologic significance of hyalinosis in the vasa recta in the medulla of allograft kidney biopsies. METHOD: We analyzed biopsy specimens from January 2010 to December 2015, obtained from both the cortex and medulla (including the vasa recta) ≥ 1 year after living-donor kidney transplantation. We excluded biopsy specimens from recipients who had undergone transplantation due to diabetic nephropathy or who had diabetes mellitus after transplantation. We evaluated hyaline arteriolopathy in the cortex using the aah score determined by the Banff 2007 classification. RESULT: Among 381 biopsy specimens obtained from 248 transplant recipients ≥ 1 year after transplantation, 36 specimens obtained from 34 recipients showed vasa recta hyalinosis (VRH) in the medulla. Among these 36 specimens, 17 had a score of aah3, 16 had a score of aah2, and 3 had a score of aah1. The incidence of VRH was 1.9% at ≥ 1 to < 4 years, 7.1% at ≥ 4 to < 8 years, and 50.0% at ≥ 8 years. The aah scores and the proportion of hyalinosis in the arteriolar media among all muscular arterioles in the cortex were significantly higher in the VRH group at ≥ 8 years in the late-phase biopsy (P < 0.01). The graft survival was worse in the VRH group (P = 0.024), although there was no significant difference in the graft survival between the ≥ aah2 and < aah2 groups at ≥ 8 years in the late-phase biopsy (P = 0.159). CONCLUSION: VRH in renal allografts reflects severe arteriolopathy of the cortex. VRH in the late-phase biopsy may be a prognostic factor for graft survival.

Interlobular hyaline arteriopathy reflects severe arteriolopathy in renal allografts.

AIM: The present study was performed to examine the clinicopathological significance of hyaline deposits in the smooth muscle of the interlobular artery (interlobular hyaline arteriopathy [IHA]) in renal allografts. METHODS: Tissue specimens that included the interlobular artery from biopsies performed from January 2012 to December 2015, as well as specimens from biopsies performed ≥1 year after living kidney transplantation were analyzed. Biopsies of recipients with new-onset diabetes mellitus after transplantation were excluded, as well as those of recipients who had undergone transplantation because of diabetic nephropathy. Arteriolopathy was evaluated using the aah score determined by the Banff 2007 classification. RESULTS: In total, 51 specimens with IHA lesions were identified among 381 biopsies obtained from 243 recipients performed ≥1 year after kidney transplantation. Among these 51 biopsies, 18 specimens had a score of aah3, 29 had a score of aah2, and four had a score of aah1. The incidence of IHA lesions was 3.6% at ≥1 to <4 years, 18.5% at ≥4 to <8 years, and 54.1% at ≥8 years. Older kidney grafts exhibited more IHA lesions. Among the biopsy specimens obtained ≥8 years after transplantation, no significant differences in the recipient or donor age, duration after transplantation, or prevalence of hypertension were observed between the IHA and non-IHA groups. The aah scores were significantly higher in the IHA group ≥8 years after transplantation as determined by the mean score test (P < 0.01). CONCLUSION: IHA in renal allografts is associated with severe arteriolopathy.

Dry weight targeting: The art and science of conventional hemodialysis.

Fluid volume overload is common and is associated with adverse outcomes in hemodialysis patients. Practicing physicians individually manage fluid volume balance in their dialysis patients according to blood pressure, interdialytic weight gain, cardiac function, nutritional status, and other comorbidities. However, accurate assessment of fluid volume status remains a concern. Indicators of dry weight target have been explored further with newer concepts and technologies. In general, total body water comprises approximately 50%-60% of adult body weight (range, 45%-75%), and water comprises 73.3% of lean body mass. The standard hydration status between intracellular water and extracellular water is maintained at a ratio of 62:38 in healthy adults, which, however, is influenced universally by body cell volume driven by age and muscle mass. Fluid volume imbalance in dialysis patients also is characterized primarily by decreased body cell mass associated with aging and muscle attenuation, as well as excess extracellular water content associated with sodium retention, which may be associated with the reserve capacity for volume overload. Indeed, dialysis patients with a leaner body mass have a higher prevalence of hypertension, poorer hypertension control, and greater left ventricular hypertrophy. Understanding of these body composition changes by aging and sarcopenia can aid clinical decision making in the dry weight assessments in dialysis patients. Advising patients with consistently high interdialytic weight gain to practice salt restriction and providing appropriate nutritional support for malnourished patients with downward trajectory in their dry weight would be of great help to achieve optimal fluid volume status.

Changes in the fluid volume balance between intra- and extracellular water in a sample of Japanese adults aged 15-88 yr old: a cross-sectional study.

The fluid volume balance between intracellular water (ICW) and extracellular water (ECW) gradually changes with age and various medical conditions. Comprehension of these physiological changes would aid in clinical decision-making related to body fluid assessments. A total of 1,992 individuals (753 men and 1,239 women) aged ≥15 yr included in this study had their body composition measurements performed at training gyms in 2014. We developed a regression formula to assess the association of age with the ratio of ECW to ICW in these subjects. The mean ages of male and female subjects were 51.2 ± 15.2 and 57.4 ± 15.2 yr, and their mean body mass indexes were 23.4 ± 3.3 and 21.1 ± 2.8 kg/m2, respectively. The total fluid volumes of male and female subjects were 39.6 ± 4.9 and 27.7 ± 3.0 liters, whereas the percent body fat mass per kilogram of body weight were 19 and 26%, respectively. The ECW-to-ICW ratio increased with age because of the steeper decrease in the ICW content than in the ECW content, especially after the age of 70 yr. The regression formulas used for calculating the age-adjusted ECW/ICW ratio were as follows: 0.5857 + 7.4334 × 10-6 × (age)2 in men and 0.6062 + 5.5775 × 10-6 × (age)2 in women. In conclusion, the fluid imbalance between ICW and ECW contents is driven by decreased cell volume associated with aging and muscle attenuation. Therefore, our proposed formula may serve as a useful assessment tool for the calculation of body fluid composition.

Association between Low Dietary Protein Intake and Geriatric Nutrition Risk Index in Patients with Chronic Kidney Disease: A Retrospective Single-Center Cohort Study.

Reduced dietary protein intake in malnourished patients with chronic kidney disease (CKD) may be associated with adverse clinical outcomes, which may mask any efficacy of a low-protein diet. The study included 126 patients with CKD who attended a dedicated dietary counseling clinic in 2005-2009 and were systematically followed until January 2015. Of these patients, 20 (15.9%) had moderate or severe nutrition-related risk of geriatric nutritional risk index (GNRI) < 92; these patients were more likely to be older, have a greater proteinuria, and have lower body mass index and serum albumin concentration. Dietary protein intake was significantly lower in older patients (r = -0.33, p < 0.001) and those with lower glomerular filtration rate (r = 0.47, p < 0.001). The non-protein to nitrogen calorie ratio was independently associated with GNRI. Reduced GNRI was significantly associated with mortality (hazard ratio (HR) = 4.94; 95% confidence interval (CI) = 1.61-15.42, p = 0.012) and cardiovascular events (HR = 9.37; 95% CI = 2.49-37.34, p = 0.006), but not with adverse renal outcomes. Restricting protein intake may be harmful to patients with any nutrition-related risk, suggesting that improvement of nutritional status should be a high priority.

Brain Natriuretic Peptide and Body Fluid Composition in Patients with Chronic Kidney Disease: A Cross-Sectional Study to Evaluate the Relationship between Volume Overload and Malnutrition.

BACKGROUND/AIM: Fluid volume overload occurs in chronic kidney disease (CKD), leading to the compensatory release of natriuretic peptides. However, the elevated cardiac peptides may also be associated with malnutrition as well as volume overload. METHODS: Body fluid composition was measured in 147 patients with CKD between 2009 and 2015, and its relationship to brain natriuretic peptide (BNP) levels was examined. Body fluid composition was separated into three components: (a) a water-free mass consisting of muscle, fat, and minerals; (b) intracellular water (ICW) content, and (c) extracellular water (ECW) content. Excess fluid mass was calculated using Chamney's formula. RESULTS: The measured BNP levels in the tertile groups were 10.9 ± 5.4, 36.3 ± 12.5, and 393 ± 542 pg/ml, respectively. Patients in a higher log-transformed BNP level tertile were more likely to be older, to have a higher frequency of cardiac comorbidities, pulse pressure, C-reactive protein levels, and proteinuria, and to have lower serum sodium, kidney function, and serum albumin (p < 0.05). In body fluid composition, decreased body mass was significantly associated with the ECW-to-ICW ratio in relation to the downward ICW slope (r = -0.235, p = 0.004) and was strongly correlated with excess fluid mass (r = -0.701, p < 0.001). The ECW-to-ICW ratio and excess fluid mass was independently associated with the BNP levels. CONCLUSION: Fluid volume imbalance between intra- and extracellular water regulated by decreased cell mass was independently associated with BNP levels, which may explain the reserve capacity for fluid accumulation in patients with CKD.

ACE and ACE2 in kidney disease.

Renin angiotensin system (RAS) activation has a significant influence on renal disease progression. The classical angiotensin-converting enzyme (ACE)-angiotensin II (Ang II)-Ang II type 1 (AT1) axis is considered to control the effects of RAS activation on renal disease. However, since its discovery in 2000 ACE2 has also been demonstrated to have a significant impact on the RAS. The synthesis and catabolism of Ang II are regulated via a complex series of interactions, which involve ACE and ACE2. In the kidneys, ACE2 is expressed in the proximal tubules and less strongly in the glomeruli. The synthesis of inactive Ang 1-9 from Ang I and the catabolism of Ang II to produce Ang 1-7 are the main functions of ACE2. Ang 1-7 reduces vasoconstriction, water retention, salt intake, cell proliferation, and reactive oxygen stress, and also has a renoprotective effect. Thus, in the non-classical RAS the ACE2-Ang 1-7-Mas axis counteracts the ACE-Ang II-AT1 axis. This review examines recent human and animal studies about renal ACE and ACE2.

Association between ratio of measured extracellular volume to expected body fluid volume and renal outcomes in patients with chronic kidney disease: a retrospective single-center cohort study.

BACKGROUND: Excess extracellular volume is a major clinical problem in patients with chronic kidney disease (CKD). However, whether the extracellular volume status is associated with disease progression is unclear. We investigated the association between the extracellular volume status and renal outcomes. METHODS: We performed a retrospective cohort study of 149 patients with CKD who underwent bioelectrical impedance analysis (BIA) from 2005 to 2009. Patients were categorized according to tertiles of extracellular volume status. The extracellular volume status was assessed by examining the ratio of extracellular water measured by BIA (ECWBIA) to the total body water calculated using the Watson formula (TBWWatson). The main outcomes were adverse renal outcomes as defined by a decline of ≥50% from the baseline glomerular filtration rate or initiation of renal replacement therapy. RESULTS: A higher %ECWBIA/TBWWatson ratio tended to be associated with older age, male sex, diabetes mellitus, resistant hypertension, lower renal function, lower serum albumin levels, higher proteinuria levels, and a higher frequency of furosemide use. In the multivariate analysis, proteinuria remained independently associated with the %ECWBIA/TBWWatson ratio. Both the intracellular and extracellular water volumes decreased with age (correlation between ICW and age, r=-0.30, P<0.001; correlation between ECW and age, r=-0.17, P=0.03). Consequently, the %ECWBIA in the body fluid composition increased with age. During a median follow-up of 4.9 years, patients in the highest tertile of the %ECWBIA/TBWWatson ratio were at greater risk of adverse renal outcomes (16.6 per 100.0 patient years) than were those in the lowest tertile (8.1 per 100.0 patient years) or second tertile (5.6 per 100.0 patient years) (log-rank P=0.005). After adjustment for covariates, the %ECWBIA/TBWWatson ratio was significantly associated with adverse renal outcomes (hazard ratio, 1.21; 95 % confidence interval, 1.10-1.34; P<0.001). CONCLUSIONS: The ECWBIA/TBWWatson ratio was independently associated with adverse renal outcomes. Proteinuria was independently associated with the extracellular volume status. The balance between ICW and ECW changes with age in that the percentage of ECW content in the body fluid composition increases. Elderly patients with CKD may thus be susceptible to volume overload.

Focal Segmental Glomerulosclerosis Secondary to Juxtaglomerular Cell Tumor during Pregnancy: A Case Report.

Juxtaglomerular cell tumor is a rare renal neoplasm. Secondary hypertension with juxtaglomerular cell tumor can be seen in females in their 20s and 30s. We present a case of juxtaglomerular cell tumor during pregnancy. A 32-year-old female was hospitalized for refractory hypertension and nephrotic syndrome in the 23rd gestational week. One year before admission, she had been diagnosed with hypertension; plasma renin activity at that time had been 2.3 ng/ml/h. Her blood pressure was uncontrolled during pregnancy, and proteinuria was detected in the 12th gestational week despite the administration of antihypertensive medications. Laboratory data showed proteinuria, hypokalemia, and hypoalbuminemia. In the 25th gestational week, she underwent surgical termination of the pregnancy because of congestive heart failure and acute renal injury. After the termination of the pregnancy and the delivery of a viable fetus, her hypertension and nephrotic syndrome were found to persist with a high plasma renin activity (13 ng/ml/h). Ultrasonography showed a 5.5-cm left renal cystic mass with a partially solid component at the lower renal pole. The left kidney with the renal mass was excised by laparoscopic nephrectomy. Plasma renin activity normalized the next day, with a decrease in blood pressure to 120-130/80-90 mm Hg; however, proteinuria remained at ≥3.5 g/day. On the basis of histopathological findings, the patient was diagnosed with a juxtaglomerular cell tumor and focal segmental glomerulosclerosis. Juxtaglomerular cell tumor is a rare renin-secreting tumor associated with refractory hypertension in young females and is a possible cause of hypertension during pregnancy.

Assessment of body composition using dry mass index and ratio of total body water to estimated volume based on bioelectrical impedance analysis in chronic kidney disease patients.

OBJECTIVE: Body mass index (BMI) is commonly used for assessment of nutritional status. However, changes in BMI in chronic kidney disease (CKD) patients are affected not only by muscle and fat but also by fluid volume. The ratio of extracellular water (ECW(BIA)) to total body water (TBW(BIA)) in multifrequency bioelectrical impedance analysis is commonly used for assessing abnormal fluid status. This study reexamines ECW(BIA)/TBW(BIA) and evaluates the reliability of TBW(BIA)/TBW(watson) and dry mass index (DMI) in the assessment of fluid and nutritional status. DESIGN, SETTING, AND SUBJECTS: TBW(BIA), intracellular water (ICW(BIA)), and ECW(BIA) were measured in 45 randomly selected CKD patients. Participants were surveyed for age, gender, BMI, blood pressure, serum albumin, estimated glomerular filtration rate, and proteinuria. DMI was calculated by the formula ([weight--TBW(BIA)]/height(2)) and TBW(BIA)/TBW(watson) using an anthropometric formula (Watson). Fluid and nutritional status were assessed using ECW(BIA)/TBW(BIA), TBW(BIA)/TBW(watson), and DMI. RESULTS: TBW(BIA)/TBW(watson) positively correlated with weight, BMI, and diastolic blood pressure and negatively correlated with age and serum albumin level. In contrast, ECW(BIA)/TBW(BIA) correlated with ICW deficit, aging, and body weight loss. On the basis of DMI and TBW(BIA)/TBW(watson), participants were categorized as follows: 1 obese patient with hypovolemia and 2 with euvolemia; 17 overweight patients with hypovolemia (n = 6), euvolemia (n = 8), or hypervolemia (n = 3); 24 patients of optimal weight with hypovolemia (n = 10), euvolemia (n = 9), or hypervolemia (n = 5); and 1 underweight patient with euvolemia. CONCLUSIONS: A combination of DMI, BMI, and TBW(BIA)/TBW(watson) makes it possible to include assessment of fluid volume to the physique index. In addition, ECW(BIA)/TBW(BIA) is not a reliable marker of edematous state in CKD patients.