2-microglobulin Concentrations Research Articles

#648 Relationship between renal tubular damage, interstitial fibrosis and semaphorin class 3C

Abstract Background and Aims The detailed mechanism of interstitial fibrosis in CKD has not been clarified. In this study, we focused on semaphorin class 3C (SEMA3C), a secreted protein expressed in the renal tubules, that is involved in embryonic kidney development [1], and investigated the relationship between SEMA3C and renal tubular damage and interstitial fibrosis. Methods < Clinical research> We investigated the correlation between serum SEMA3C concentration and the renal tubular damage marker urinary β2 microglobulin (β2MG) concentration in the 191 patients who underwent kidney biopsy from 2017 to 2021 at Yamagata University. < In vivo study> We generated proximal tubule-specific SEMA3C knockout mice (PT-SEMA3C KO) from male mice (C57BL/6) using the Cre/loxP system. The PT-SEMA3C KO group and control group were fed a 0.2% adenine diet for 5 weeks to induce CKD. The area of interstitial fibrosis/tubular atrophy (IFTA) region was assessed by Masson-Trichrome staining. Results < Clinical research> The median age of the patients was 54 (IQR 38-68) years, 94 men and 97 women. Median serum SEMA3C concentration was 0.14 (IQR 0.07-0.35) ng/ml. Median urinary β2MG levels was 0.22 (IQR 0-1.79) mg/gCr. Spearman's correlation analysis showed a significant negative correlation between serum SEMA3C and urinary β2MG levels (r=-0.208, P=0.005), but no correlation between eGFR and Urinary protein/ creatinine. < In vivo study> IFTA region was 5.6% in the control group, compared to 11.2% in the PT-SEMA3C KO group (p=0.031). Interstitial fibrosis was significantly suppressed in the PT-SEMA3C KO mice (Fig. 1). Conclusion Our clinical and in vivo results indicate that serum SEMA3C is associated with renal tubular damage and interstitial fibrosis.

Correlation between nerve conduction changes and BETA-2 microglobulin concentration in chronic kidney disease patients on hemodialysis combined with hemodiafiltration online.

This study aimed to investigate the correlation between beta-2 microglobulin (B2M) concentration and some nerve conduction indices and evaluate the changes in some nerve conduction indices after treatment with hemodialysis (HD) combined with hemodiafiltration online in end-stage renal disease patients. From July 2021 to July 2022, a cross-sectional study was conducted on 80 end-stage renal disease patients on HD at Can Tho General Hospital, Viet Nam. All the patients had B2M testing and nerve conduction measurements. Patients with nerve conduction disorders were treated and remeasured after 6 months to evaluate the treatment results. At baseline, there was a moderate negative correlation between B2M and the tibial nerve and motor branch of the ulnar conduction velocity (V) (r = -0.305 and -0.315, P < .05). There was a moderate positive correlation between B2M and motor latency of the tibial and peroneal nerve (r = 0.434 and 0.440, P < .05). After 6 months of using the combination of HD and hemodiafiltration online, the V (31.3 ± 7.96 up to 44.88 ± 9.67 m/s) and the amplitude (A) (1.71 ± 1.16 up to 2.61 ± 1.51 mV) of the peroneal nerve increased, the motor latency decreased (8.21 ± 2.65 down to 5.23 ± 3.58 ms). With the tibial nerve, motor conduction V increased from 30.53 ± 8.05 m/s to 43.56 ± 8.99 m/s and the A increased from 5.04 ± 3.16 mV to 7.75 ± 4.45 mV. With the ulnar nerve, the A increased, and motor latency decreased after 6 months. The nerve conduction indices also improved significantly in the median nerve.

Association of Beta-2 Microglobulin with Stroke and All-Cause Mortality in Adults Aged ≥40 in U.S.: NHANES III.

Stroke is the predominant cause of death worldwide. We aimed to investigate the association of serum beta-2 microglobulin ( 2M) concentrations with risk of stroke and all-cause mortalities in a cohort study. Overall, 4914 U.S. adults (mean age = 63.0 years, 44.3% male) were recruited from the National Health and Nutrition Examination Survey (NHANES Ⅲ). During a median follow-up of 19.4 years, 254 stroke deaths and 3415 all-cause deaths were identified by the National Center for Health Statistics. The associations of 2M with stroke and all-cause mortalities were investigated by using weighted Cox proportional hazard regression models. 2M was positively associated with stroke and all-cause mortality in unadjusted models and multivariable-adjusted models. The multivariable HR (95% CI) for stroke mortality in Q5 VS Q1 of serum 2M concentrations was 3.45 (1.33-8.91; p for trend = 0.001) and that for all-cause mortality was 3.95 (3.05-5.12; p for trend 0.001). In subgroup analyses, the association of 2M and stroke mortality did not vary by different levels of sociodemographic and general stroke risk factors (p interaction 0.05). In addition, the magnitude of positive association between 2M with all-cause mortality did vary by age, ratio of family income to poverty, smoking status, and history of hypertensive (p interaction 0.05). Our findings suggest that support that 2M may be a marker of stroke and all-cause mortality, which provides a new perspective for the study of cerebrovascular health and long-term survival in the future.

Waldenström macroglobulinemia: 2023 update on diagnosis, risk stratification, and management.

Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity. Presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. The L265P mutation in MYD88 is detectable in more than 90% of patients and is found in most IgM MGUS patients. MYD88 is not required for the diagnosis. Age, hemoglobin level, platelet count, β2 microglobulin, LDH, and monoclonal IgM concentrations are characteristics that are predictive of outcomes. Not all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop. Rituximab-monotherapy is inferior to regimens that combine it with bendamustine, an alkylating agent, a proteosome inhibitor, or a BTK inhibitor. The preferred Mayo Clinic induction is either rituximab and bendamustine (without rituximab maintenance) or zanubrutinib. Bortezomib, cyclophosphamide, fludarabine, thalidomide, everolimus, Bruton Tyrosine Kinase inhibitors, carfilzomib, lenalidomide, bendamustine, and venetoclax have all been shown to have activity in relapsed WM. Given WM's natural history, the reduction of therapy toxicity is an important part of treatment selection.

ODP250 The Role of Urine Renal Injury Markers in Obese Children and Adolescents with Diabetes Mellitus

Abstract Backgrounds Diabetic children especially who are obese lead to poor glycemic control thus are at higher risk for early microvascular complications. Renal tubulointerstitial markers play integral role in the evaluation of diabetic nephropathy and various biomarkers have been proposed. Yet, their role in obese pediatric population is uncertain. The aim of this study is to investigate renal injury markers in children with diabetes mellitus (DM) in relation with obesity and determine their role for early predictor of diabetic complications. Methods Fifty-three children and adolescents diagnosed with either type 1 or 2 DM and 44 controls aged 7-18 years were included. Clinical and laboratory characteristics including renal injury markers among subjects were compared with respective to body mass index (BMI), presence and type of DM. Results Urine neutrophil gelatinase associated lipocalin and kidney injury molecule-1 were lower whereas beta-2 microglobulin and n-acetylglucosamine (NAG) concentrations were higher in controls compared to diabetic children. None of renal injury markers showed significant difference between normoweight and obese children. In multiple regression analyses, urine NAG was associated with HbA1c and the presence of DM while high homeostatic model assessment of insulin resistance was identified as a risk factor of for increased urine NAG in type 2 diabetic children. Conclusion Urine NAG could be a marker associated not only with diabetic nephropathy, but also with insulin resistance regardless of BMI. Presentation: No date and time listed

Urine Biomarkers of Kidney Tubule Health, Injury, and Inflammation are Associated with Progression of CKD in Children.

Novel urine biomarkers may improve identification of children at greater risk of rapid kidney function decline, and elucidate the pathophysiology of CKD progression. We investigated the relationship between urine biomarkers of kidney tubular health (EGF and α-1 microglobulin), tubular injury (kidney injury molecule-1; KIM-1), and inflammation (monocyte chemoattractant protein-1 [MCP-1] and YKL-40) and CKD progression. The prospective CKD in Children Study enrolled children aged 6 months to 16 years with an eGFR of 30-90ml/min per 1.73m2. Urine biomarkers were assayed a median of 5 months [IQR: 4-7] after study enrollment. We indexed the biomarker to urine creatinine by dividing the urine biomarker concentration by the urine creatinine concentration to account for the concentration of the urine. The primary outcome was CKD progression (a composite of a 50% decline in eGFR or kidney failure) during the follow-up period. Overall, 252 of 665 children (38%) reached the composite outcome over a median follow-up of 6.5 years. After adjustment for covariates, children with urine EGF concentrations in the lowest quartile were at a seven-fold higher risk of CKD progression versus those with concentrations in the highest quartile (fully adjusted hazard ratio [aHR], 7.1; 95% confidence interval [95% CI], 3.9 to 20.0). Children with urine KIM-1, MCP-1, and α-1 microglobulin concentrations in the highest quartile were also at significantly higher risk of CKD progression versus those with biomarker concentrations in the lowest quartile. Addition of the five biomarkers to a clinical model increased the discrimination and reclassification for CKD progression. After multivariable adjustment, a lower urine EGF concentration and higher urine KIM-1, MCP-1, and α-1 microglobulin concentrations were each associated with CKD progression in children.

Treatment and outcome patterns of patients with Waldenström’s macroglobulinemia: a large, multicenter retrospective review in China

In this study, we aimed to investigate treatment options and the prognosis of patients with WM in China. This retrospective study included 1141 patients diagnosed with symptomatic WM between January 2003 and December 2019 at 35 tertiary hospitals in 22 provinces of China. Fifty-four patients (7.3%) received monotherapy, 264 (36.0%) received chemoimmunotherapy, 395 (53.8%) received other combination regimens without rituximab, and 21 (2.9%) received ibrutinib. Using a multivariable Cox regression model, age > 65 years old, platelets <100 × 109/L, serum albumin <3.5 g/dl, β2 microglobulin concentration ≥4 mg/L and LDH ≥250 IU/L predicted poor OS. In summary, our study showed that frontline treatment choices for WM are widely heterogeneous. We validated most of the established prognostic factors in the rIPSS (age >65 years, LDH ≥250 IU/L, ALB <3.5 g/dl and β2 microglobulin ≥4 mg/L) together with PLT ≤ 100 × 109/L indicate a poor prognosis for patients with WM.

Waldenström macroglobulinemia: 2021 update on diagnosis, risk stratification, and management.

Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity. Presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. The L265P mutation in MYD88 is detectable in more than 90% of patients and is found in the majority of IgM MGUS patients. Age, hemoglobin level, platelet count, β2 microglobulin, LDH and monoclonal IgM concentrations are characteristics that are predictive of outcomes. Not all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop. Rituximab-monotherapy is inferior to regimens that combine it with bendamustine, an alkylating agent, a proteosome inhibitor, or ibrutinib. Purine nucleoside analogues are active but usage is declining in favor of less toxic alternatives. The preferred Mayo Clinic induction is rituximab and bendamustine. Bortezomib, fludarabine, thalidomide, everolimus, Bruton Tyrosine Kinase inhibitors, carfilzomib, lenalidomide, and bendamustine have all been shown to have activity in relapsed WM. Given WM's natural history, reduction of therapy toxicity is an important part of treatment selection.

High-Volume Hemodiafiltration Reduces Pre-Dialysis Beta-2 Microglobulin Concentration Compared with High-Flux Hemodialysis: A Post Hoc Analysis of the HDFit Trial

High-Volume Hemodiafiltration Reduces Pre-Dialysis Beta-2 Microglobulin Concentration Compared with High-Flux Hemodialysis: A Post Hoc Analysis of the HDFit Trial

Relationship between urinary β2 -microglobulin concentration and mortality in a cadmium-polluted area in Japan: A 35-year follow-up study.

The relationship between urinary β2 -microglobulin (β2 -MG) and the risk of all-cause mortality and cause-specific mortality in a cadmium (Cd)-polluted area was investigated in 3139 inhabitants (1404 men and 1735 women) of the Kakehashi River basin in Japan at 35-year follow-up. The subjects had been participants in the 1981-1982 health impact survey that assessed Cd-induced renal dysfunction, as measured by the urinary β2 -MG concentration. Hazard ratios were calculated to assess the risk of all-cause and cause-specific mortality according to the urinary β2 -MG concentrations. Risk ratios (RRs) were assessed using the Fine and Gray regression model to account for competing risks of cause-specific mortality. The mortality rate was significantly higher in participants with urinary β2 -MG concentrations >1000 μg/g creatinine (Cr) for men and >300 μg/g Cr for women. In the proportional hazard model, higher urinary β2 -MG concentrations were associated with higher risks of circulatory disease, digestive system diseases, and kidney and urinary tract diseases in men and women, and with senility for women. However, when competing risk was accounted for, the RRs were significantly higher only for kidney and urinary tract diseases in men and women (RR for each increment of 1000 μg/g Cr [95% confidence interval]: 1.02 [1.00-1.04] for men, and 1.01 [1.00-1.02] for women). The long-term prognosis of participants with renal tubular dysfunction was poor, most likely due to kidney and renal tract diseases.

Predicting 3-year mortality based on the tumor necrosis factor alpha concentration in low-flux hemodialysis patients.

Tumor necrosis factor alpha (TNF-α) is an inflammatory cytokine produced during acute inflammation. Few studies have evaluated the association between serum TNF-α and its receptors and their clinical outcomes in hemodialysis patients. However, a study assessing patients using a low-flux dialyzer reuse has not been conducted yet. The serum TNF-α concentrations of 319 prevalent hemodialysis patients (mean age, 45 ± 15 years; median duration of hemodialysis, 48 [interquartile range, 26-79] months; 185 males and 134 females) was examined to predict their 3-year mortality. The patients were divided into tertiles according to their serum TNF-α concentrations: T1 (n = 106; serum TNF-α concentration, <41.22 pg/mL), T2 (n = 106; serum TNF-α level, from 41.22 to 67.28 pg/mL), and T3 (n = 107; serum TNF-α concentration, ≥ 67.29 pg/mL). During the 36-month follow-up period, a total of 50 (15.7%) patients died from all causes. The Kaplan-Meier analysis revealed that the all-cause mortality in T3 was significantly higher compared to that in T1 and T2 (log-rank test, P < .001). The serum TNF-α level was a significant predictor for all-cause mortality (area under the curve = 0.887, P < .001, cutoff value, 89.812 pg/mL, sensitivity = 76%, specificity = 96.3%). The serum TNF-α level was a better predictor of mortality than the duration of hemodialysis and serum albumin, serum high-sensitivity C-reactive protein, and serum beta-2 microglobulin concentrations. The serum TNF-α concentration was a good predictor of the 3-year mortality in low-flux hemodialysis patients.

Evaluation of the prognostic and predictive value of free light chains in patients with chronic lymphocytic leukemia – preliminary results

AbstractIntroductionκ and λ serum free light chains (sFLCs) are produced during physiological lymphopoesis by plasmocytes and B lymphocytes in a constant ratio related to heavy chains. The measurement of sFLC plays an important role in the diagnosis and monitoring of patients with multiple myeloma (MM). The first reports suggested that sFLC disturbances might have prognostic value also in patients with chronic lymphocytic leukemia (CLL). Aim of the study: The aim of the study was to evaluate the relationship between sFLC concentration and recognized prognostic factors and clinical course of CLL. Materials and methods: The sFLC concentration was measured using a latex-enhanced immunoassay in 59 patients with newly diagnosed CLL. The relationship between sFLC concentration and time to start of the treatment (TFT), the response rate to therapy (ORR) and overall survival (OS) was assessed.ResultsA significant correlation was found between sFLC κ concentration and the clinical stage of leukemia according to Rai classification, β-2 microglobulin concentration, LDH activity, CD38 expression, as well as between sFLC λlevel and β-2 microglobulin concentration and platelet count (PLT ). There was also a correlation between the values of summated κ and λ and the clinical stage of disease according to Rai classification, β-2 microglobulin concentration, CD38 expression, white blood cells count (WBC), lymphocyte count (ALC) and hemoglobin (Hgb) concentration. The κ/λ ratio (FCLR) values were significantly different in the CD38+ and CD38- population.SummarySimple and reproducible clonality index, which constitutes the sFLC concentration assessment, can be an attractive, potential prognostic marker in patients with CLL, however further studies are needed on a larger group of patients especially in relation to the predictive value of sFLC.

Squared frequency-Kt/V: a new index of hemodialysis adequacy\u2014correlation with solute concentrations by computer simulation

BackgroundIn patients undergoing home dialysis, conventionally, Kt/V has been regarded as an index of the removal efficiency per dialysis session. However, more recently, it has been considered that the hemodialysis product (HDP), rather than the Kt/V, is better associated with the clinical symptoms and outcomes in patients undergoing short daily dialysis or nocturnal dialysis. Nevertheless, the HDP lacks a theoretical background, and it does not take into consideration the dialyzer clearance or patient’s body size. The aims of the present study were to clarify the theoretical validity of HDP focusing on its association with solute concentration by computer simulation and to propose a new index of hemodialysis adequacy.MethodsWe used compartment models and calculated the time course of urea and β2 microglobulin (β2MG) concentrations to determine the peak concentrations and time-averaged concentrations at varying dialysis frequencies (n = 2–7 sessions/week) and durations of dialysis per session (t = 1 to 8 h dialysis sessions).ResultsIt was found that the peak concentrations of urea and β2MG were significantly correlated with the HDP. Based on this, we theoretically extracted the factor related to the peak concentration and defined the squared frequency-Kt/V (sf-Kt/V), as a new index for determining hemodialysis adequacy (sf-Kt/V = n2Kt/V; K, clearance; V, solute distribution volume; n, frequency; t, dialysis time); this index was well correlated with the peak concentrations of urea and β2MG, even when the values of K and V were changed.ConclusionsSince the sf-Kt/V is an index that reflects peak concentrations of urea and β2MG, which takes into account the dialysis frequency, session duration, dialyzer clearance, and the body weight of the patient, it will be a very useful tool for determining appropriate dialysis schedules and dialysis conditions for individual patients.

Observation of lenalidomide combined with modified MP regimen in the treatment of elderly patients with multiple myeloma

Objective To investigate the clinical effect of lenalidomide combined with modified MP regimen in the treatment of multiple myeloma(MM). Methods Eighty=four elderly multiple myeloma patients treated in Tangshan City Workers' Hospital from January 2013 December 2016 were enrolled in this study.The patients were randomly divided into treatment group (42 cases) and control group (42 cases). The patients in the treatment group were given LMP regimen + α2b- interferon.The patients in the control group received the standard MPT regimen.The changes of the level of β 2 microglobulin in the two groups before and after treatment were compared, and the total effective rate in the two groups was compared. Results No statistically significant difference was showed between the two groups in β 2 microglobulin before treatment (P>0.05). After treatment, β 2 microglobulin concentration in the treatment group was (3.11±0.28) and was (4.75±0.36) in the control group, there was significant difference between two groups (t=9.094, P<0.05); the total effective rate of the treatment group was 83.33%, 59.52% in the control group, there was significant difference between two groups (t=5.833, P=0.016). The incidence of adverse reactions in the treatment group was 9.52%, the control group was 26.19%, and the two groups were statistically significant (t=3.977, P=0.046). Conclusion The clinical effect of Lenalidomide combined with modified MP regimen in the treatment of MM is better than that of conventional treatment, the total effective rate is highwe, with less adverse reactions. Key words: Lenalidomide; MP regimen; Multiple myeloma; Elderly; β2 microglobulin

Proteinuria and the Clinical Course of Dobrava-Belgrade Hantavirus Infection

Purpose: Human infection with Dobrava-Belgrade virus (DOBV) in Northern Germany causes a mild form of hantavirus disease predominantly characterized by acute kidney injury due to interstitial nephritis. We evaluated the largest number of DOBV-infected patients so far regarding clinical course, proteinuria, and prognostic markers. Patients and Methods: Patients with DOBV-associated hantavirus disease admitted to the Renal Division of the University of Lübeck (Germany) between 1997 and 2012 were included in this study. Symptoms, clinical course, laboratory parameters, and urinary protein analysis were investigated at admission (baseline, t₀), 3–5 days (t_3–5), 10–17 days (t_10–17), and after 1 year of follow-up (t₃₆₅). Results: Of the 34 patients (male/female ratio: 23/11; age: 41 ± 14 years) included in the study, 4 underwent hemodialysis (HD). Glomerular filtration rate was 17 ± 14 mL/min at t₀ and increased to 27 ± 26 mL/min (t_3–5), 57 ± 20 mL/min (t_10–17), and 84 ± 16 mL/min (t₃₆₅). Albuminuria and tubular proteinuria (α₁- and β₂-microglobulin) decreased during follow-up; the urinary α₁-microglobulin concentration in patients who required HD was significantly higher than that in patients not requiring HD (t₀: 186 ± 51 vs. 45 ± 26 mg/g creatinine; t_3–5: 87 ± 14 vs. 32 ± 16 mg/g creatinine; t_10–17: 63 ± 18 vs. 28 ± 12 mg/g creatinine; p < 0.001). Conclusions: DOBV infection of inpatients in Northern Germany is associated with severe kidney injury that recovers within a few weeks and normalizes within 1 year. Tubular proteinuria is associated with the severity of kidney injury and the necessity of renal replacement therapy in these DOBV-infected patients.

Waldenström macroglobulinemia: 2017 update on diagnosis, risk stratification, and management.

Presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. The L265P mutation in MYD88 is detectable in more than 90% of patients. Risk Stratification: Age, hemoglobin level, platelet count, β2 microglobulin, and monoclonal IgM concentrations are characteristics required for prognosis. Risk-Adapted Therapy: Not all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop. Rituximab-based therapy is used in virtually all U.S. patients with WM and can be combined with bendamustine, an alkylating agent, or a proteosome inhibitor. Purine nucleoside analogues are widely used in Europe. The preferred Mayo Clinic nonstudy therapeutic induction is rituximab and bendamustine. Potential for stem cell transplantation should be considered in induction therapy selection. Management of Refractory Disease: Bortezomib, fludarabine, thalidomide, everolimus, ibrutinib, carfilzomib, lenalidomide, and bendamustine have all been shown to have activity in WM. Given WM's natural history, reduction of complications will be a priority for future treatment trials. Am. J. Hematol. 92:209-217, 2017. © 2016 Wiley Periodicals, Inc.

SY-1-1 - Urinary biomarkers of acute kidney injury in anti-cancer drug treatment

Clinically acute kidney injury (AKI) is characterized by a rapid reduction in kidney function resulting in a failure to maintain fluid, electrolyte and acid-base homeostasis. The traditionally used markers to detect and monitor the progression of AKI, including serum creatinine, creatinine clearance and blood urea nitrogen levels, are insensitive and nonspecific. Until now, urinary biomarkers to detect AKI were reported such as kidney injury molecule (KIM) 1, neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemotactic protein (MCP)-1. However, whether these urinary biomarkers can detect drug-induced AKI accurately in the clinical settings remains unclear. Therefore, in the present study, we examined whether the recently discovered urinary biomarkers for AKI can detect cisplatin-induced nephrotoxicity in patients with lung cancer. Among several potential biomarkers, we measured KIM-1, MCP-1, NGAL, N-acetyl-β-D-glucosaminidase, and β 2-microglobulin concentrations in urine samples from 11 patients with lung cancer. These samples were collected the day before cisplatin administration and on days 3, 7, and 14 after the administration. Receiver operating characteristics curve analyses revealed that KIM-1 and MCP-1, but not NGAL, could detect AKI with high accuracy (area under the curve [AUC] = 0.858, 0.850, and 0.608, respectively). The value of AUC was increased in the combination of KIM-1 and MCP-1 compared to either alone. These results suggest that some urinary biomarkers specific for each anticancer drug can help find drug-induced AKI prior to the next administration.

Effect of Treatment Duration and Frequency on Uremic Solute Kinetics, Clearances and Concentrations.

The kinetics of uremic solute clearances are discussed based on two categories of uremic solutes, namely those that are and those that are not derived directly from nutrient intake, particularly dietary protein intake. This review highlights dialysis treatments that are more frequent and longer (high-dose hemodialysis) than conventional thrice weekly therapy. It is proposed that the dialysis dose measures based on urea as a marker uremic solute, such as Kt/V and stdKt/V, be referred to as measures of dialysis inadequacy, not dialysis adequacy. For uremic solutes derived directly from nutrient intake, it is suggested that inorganic phosphorus and protein-bound uremic solutes be considered as markers in the development of alternative measures of dialysis dose for high-dose hemodialysis prescriptions. As the current gap in understanding the detailed kinetics of protein-bound uremic solutes, it is proposed that normalization of serum phosphorus concentration with a minimum (or preferably without a) need for oral-phosphorus binders be targeted as a measure of dialysis adequacy in high-dose hemodialysis. For large uremic solutes not derived directly from nutrient intake (middle molecules), use of extracorporeal clearances for β2 -microglobulin that are higher than currently available during thrice weekly therapy is unlikely to reduce predialysis serum β2 -microglobulin concentrations. High-dose hemodialysis prescriptions will lead to reductions in predialysis serum β2 -microglobulin concentrations, but such reductions are also limited by significant residual kidney clearance. Kinetic data regarding middle molecules larger than β2 -microglobulin are scarce; additional studies on such uremic solutes are of high interest to better understand improved methods for prescribing high-dose hemodialysis prescriptions to improve patient outcomes.

Renal function in children treated for central nervous system malignancies.

AimThe aim of the study was to evaluate renal function and to assess the usefulness of the following nephrotoxicity markers: cystatin C (CYS C), beta-2 microglobulin (B2MG) and neutrophil gelatinase-associated lipocalin (NGAL) in 38 (18 girls, 20 boys) children previously treated for central nervous system malignancy.MaterialMedian age at evaluation was 13.7 years (range 2.1–22 years). The mean follow-up time after the completion of chemotherapy was 3.2 years (range 0.16–6.5 years).ResultsSubclinical chronic kidney disease (estimated glomerular filtration rate: eGFR 90–60 ml/min/1.73 m2) was found in 22 patients (58 %), while renal insufficiency (eGFR 30–60 ml/min/1.73 m2) was found in six children (16 %). It has been demonstrated statistically significant negative correlation between the eGFR and cystatin C concentration (p < 0.0001) and eGFR and beta-2 microglobulin concentration (p < 0.02). Conversely, there was no correlation between eGFR and NGAL. Thirteen children (34 %) developed drug-induced tubulopathy: decreased tubular reabsorption of phosphate (TRP) and renal tubular threshold for phosphate (Tmp/GFR).ConclusionChildren treated for CNS tumours often develop drug-induced chronic renal disease, involving the glomeruli and/or renal tubules. Cystatin C and beta-2 microglobulin seemed to be good markers for chronic kidney damage in these patients, which is probably not true for NGAL.

A 28-year observational study of urinary cadmium and β2 -microglobulin concentrations in inhabitants in cadmium-polluted areas in Japan.

The biological half-life of cadmium (Cd) is as long as 10-30 years. Exposure to this element induces renal tubular dysfunction, which is considered irreversible. β2 -microglobulin (β2 -MG) is a low-molecular-weight protein, and urinary β2 -MG is one of the most useful and critical indicators for the early detection of renal tubular dysfunction. However, very little research has been published concerning the long-term observation of Cd-induced adverse health effects. As such, this follow-up study was conducted for 28 years to clarify the relationship between the concentration of Cd and β2 -MG in the urine of 28 inhabitants (14 male and 14 female) living in the Kakehashi River basin, Ishikawa prefecture (Japan), previously one of the most highly Cd-polluted regions in this country. All subjects were over 60 years old in 2014 and participated in all six health examinations conducted over 28 years (1986-2014). Urine was collected at the appropriate time and kept frozen to analyze urinary Cd and β2 -MG concentrations. The urinary Cd concentration was found to decrease by nearly half between 1986 and 2008 in both male and female subjects, whereas it increased significantly from 2008 to 2014 in males. In contrast, urinary β2 -MG concentrations tended to increase over the 28-year study period in both sexes. Urinary Cd and β2 -MG concentrations in females were significantly higher than those in males in this Cd-polluted region. Age is more strongly associated with urinary β2 -MG concentration than recent Cd body burden. Copyright © 2016 John Wiley & Sons, Ltd.