Shih-Han S. Huang

Association between water intake, chronic kidney disease, and cardiovascular disease: a cross-sectional analysis of NHANES data.

Background: Evidence from animal and human studies suggests a protective effect of higher water intake on kidney function and cardiovascular disease (CVD). Here the associations between water intake, chronic kidney disease (CKD) and CVD were examined in the general population. Methods: We conducted a cross-sectional analysis of the 2005-2006 National Health and Nutrition Examination Survey. Non-pregnant adults with an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m2 who were not taking diuretics were included. Total water intake from foods and beverages was categorized as low (<2.0 l/day), moderate (2.0-4.3 l/day) and high (>4.3 l/day). We examined associations between low total water intake and CKD (eGFR 30-60 ml/min/1.73 m2) and self-reported CVD. Results: Of 3,427 adults (mean age 46 (range 20-84); mean eGFR 95 ml/min/1.73 m2 (range 30-161)), 13% had CKD and 18% had CVD. CKD was higher among those with the lowest (<2.0 l/day) vs. highest total water intake (>4.3 l/day) (adjusted odds ratio (OR) 2.52; 95% confidence interval (CI) 0.91-6.96). When stratified by intake of (1) plain water and (2) other beverages, CKD was associated with low intake of plain water: adjusted OR 2.36 (95% CI 1.10-5.06), but not other beverages: adjusted OR 0.87 (95% CI 0.30-2.50). There was no association between low water intake and CVD (adjusted OR 0.76; 95% CI 0.37-1.59). Conclusions: Our results provide additional evidence suggesting a potentially protective effect of higher total water intake, particularly plain water, on the kidney.

Hyperfiltration Affects Accuracy of Creatinine eGFR Measurement

BACKGROUND AND OBJECTIVES Surrogate markers such as creatinine, cystatin C (CysC), and beta trace protein (BTP) have been used to estimate GFR (eGFR). The accuracy of eGFR may be altered with hyperfiltration and differences in filtration fraction (FF). It is hypothesized that the accuracy of creatinine for eGFR may be affected by hyperfiltration and different effective renal plasma flow (ERPF). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A total of 127 pediatric patients with various renal diseases underwent simultaneous measurements of GFR using 51Cr-EDTA renal scan and ERPF (131I-hippurate clearance) to calculate the FF (FF=GFR/ERPF). The eGFRs were calculated using the commonly used Schwartz (creatinine), Filler (CysC), and Benlamri (BTP) formulas. Agreement of the eGFRs with the measured isotope GFRs was assessed by Bland-Altman plots. Correlation analysis was performed using nonparametric tests to compare FF with eGFR-GFR. RESULTS The 127 children at a median age (with 25th percentile, 75th percentile) of 11.9 (8.5, 14.9) years had a mean 51Cr EDTA-GFR of 100.6±32.1 ml/min per 1.73 m2 and a median 131I-hippurate clearance (ERPF) of 588 (398,739) ml/min per 1.73 m2. Mean FF was 17.7±4.5% with no correlation between the FF and the error (eGFR-GFR) for CysC and BTP eGFR, whereas there was a significant negative correlation between the error for Schwartz eGFR and FF. CONCLUSIONS There is a significant negative correlation between the error for the Schwartz eGFR and the FF. CysC and BTP are not affected by differences in FF.

The usefulness of cystatin C and related formulae in pediatrics.

Abstract Serum creatinine does not share the properties of an ideal marker of glomerular filtration rate (GFR) like inulin, but continues to be the most widely used endogenous marker of GFR. In the search of a better biomarker of GFR, the small molecular weight protein cystatin C has been introduced with features more similar to that of inulin, such as constant production and no non-renal elimination. However, it has not enjoyed widespread use despite its significantly improved diagnostic performance in the detection of impaired GFR and its independence of body composition. A variety of formulae based on either cystatin C or creatinine or both have been developed to estimate GFR. We summarize the currently used methods of GFR measurement, their limitations and analytical errors. The review also summarizes the history, features and the feasibility of cystatin C measurements as well as the most widely used formulae for the estimation of GFR in children. The diagnostic performance of the cystatin C derived eGFR formulae at various levels of GFR is also discussed. An eGFR formula derived from pooled studies analyzing both creatinine and cystatin C, and using a biology-based mathematical approach may be advantageous.

Cystatin C Reduction Ratio Depends on Normalized Blood Liters Processed and Fluid Removal during Hemodialysis

BACKGROUND AND OBJECTIVES A negative correlation between the weekly standard Kt/V (urea) and serum cystatin C level (CysC) in functionally anephric dialysis patients has been previously demonstrated. Our objective was to measure the per dialysis CysC reduction ratio (CCRR) and to compare it with other indices of dialytic functions. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In a pilot cross-sectional study of 15 functionally anephric patients on conventional high-flux high-efficiency hemodialysis three times per week, CysC levels were drawn pre-, mid-, and postdialysis over 1 week. CCRR was compared with single-pool Kt/V (Sp Kt/V) using urea kinetic modeling, urea reduction ratio (URR), creatinine reduction ratio (CRR), normalized liters processed (LP/kg), and ultrafiltration volume (UF). Normally distributed data (Shapiro-Wilks test) were described as mean±SD, otherwise as median and interquartile range. RESULTS The mean pre- and post-CysC levels were 6.0±1.0 and 4.7±1.1 mg/L. The Sp Kt/V and Std Kt/V were 1.5±0.2 and 2.6. The URR, CRR, and CCRR were 70.2%±9.0%, 64.5%±8.2%, and 26.1%±11.8%, respectively. There was no correlation between the CCRR, and the Sp Kt/V, URR, and CRR, whereas CCRR correlated with LP/kg and UF. Multiple regression analysis with these two parameters provided a model that explained 81% of the variance. CONCLUSIONS Our data suggest that normalized liters processed and ultrafiltration volume explain most of the variance of CCRR. Therefore, CCRR may be an excellent method to monitor dialysis efficiency of low molecular weight proteins.

Euvolemia in Hemodialysis Patients: A Potentially Dangerous Goal?

Dialysis patients have high mortality rate and the leading cause of death is cardiovascular disease. Uremic cardiomyopathy differs from that due to conventional atherosclerosis, where cardiovascular changes result in ineffective circulation and lead to tissue ischemia. Modern dialysis has significant limitations with fluid management probably the most challenging. Current evidence suggests that both volume overload and aggressive fluid removal can induce circulatory stress and multi‐organ injury. Furthermore, we do not have accurate volume assessment tools. As a result, targeting euvolemia might result in more harm than benefit with conventional hemodialysis therapy. Therefore, it might be time to consider a degree of permissive over‐hydration until we have better tools to both determine ideal weight and improve current renal replacement therapy so that the process of achieving it is not so fraught with the current dangers.

Pediatric reference intervals for immunoglobulin G and its subclasses with Siemens immunonephelometric assays.

OBJECTIVE To determine the pediatric reference intervals for the Dade Behring IgG subclass reagents. DESIGN AND METHODS Blood samples of healthy children and adolescents were analyzed to determine the level of immunoglobulin G (IgG) and the IgG subclass using the reagents of Dade Behring Marburg GmbH. RESULTS The reference intervals categorized by age were reported from a total of 436 samples. There was an excellent correlation between the total IgG and the sum of the IgG subclasses. CONCLUSIONS Our data provide the missing pediatric reference intervals and enable the use of the Dade Behring nephelometric IgG subclass reagents in children and adolescents.

Plasmapheresis for the treatment of kidney diseases

The purpose of this review is to examine the evidence supporting the application of plasma exchange in renal disease. Our review focuses on the following 6 most common renal indications for plasma exchange based on 2014 registry data from the Canadian Apheresis Group: (i) thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome; (ii) renal transplantation, (iii) anti-neutrophil cytoplasm antibodies-associated vasculitis, (iv) cryoglobulinemia, (v) focal segmental glomerulosclerosis, and (vi) Goodpasture syndrome. The rarity of these diseases and their rapid, often fatal course mean that randomized controlled studies of plasma exchange are rarely conducted. Although evidence from an adequately powered randomized controlled trial supports the use of plasma exchange to treat thrombotic thrombocytopenic purpura, the use of plasma exchange to treat other renal diseases is only supported by observational and mechanistic studies. Larger well-designed trials are needed to clarify the potential role of plasma exchange in renal disease. Growing international collaboration will improve the quality of future studies in this area.

Plasma Exchange for Kidney Disease: What Is the Best Evidence?

Therapeutic plasma exchange (TPE) has been used as adjunctive therapy for various kidney diseases dating back to the 1970s. In many cases, support for TPE was on mechanistic grounds given the potential to remove unwanted large molecular-weight substances such as autoantibodies, immune complexes, myeloma light chains, and cryoglobulins. More recently, growing evidence from randomized controlled trials, meta-analyses, and prospective studies has provided insights into more rational use of this therapy. This report describes the role of TPE for the 6 most common kidney indications in the 2013 Canadian Apheresis Group (CAG) registry and the evidence that underpins current recommendations and practice. These kidney indications include thrombotic microangiopathy, antiglomerular basement membrane disease, anti-neutrophil cytoplasmic antibody-associated vasculitis, cryoglobulinemia, recurrence of focal and segmental glomerulosclerosis in the kidney allograft, and kidney transplantation.

What is the intrapatient variability of mycophenolic acid trough levels

TDM of MPA, the active compound of MMF, is rarely used despite its substantial intra‐ and interpatient variability. Little is known about the utility of long‐term MPA TDM. Data are expressed as mean (one standard deviation). All available data from 27 renal transplant recipients (mean age at transplantation: 7.7 [5.0] yr) with an average follow‐up of 9.3 (4.6) yr were analyzed. MPA levels were measured using the EMIT. GFR was measured using cystatin C and eGFR was calculated using the Filler formula. Intrapatient CV of the trough level was calculated as the ratio of the mean divided by one standard deviation. Mean cystatin C eGFR was 56.9 (24.4) mL/min/1.73 m2. There was a weak but significant correlation between the MPA trough level and the AUC (Spearman r = 0.6592, p < 0.0001). A total of 1964 MPA trough levels (73 [45]/patient) were measured, as compared to 3462 Tac trough levels (144 [71]/patient). The average MPA trough level was 3.01 (1.26) mg/L and the average trough Tac level was 7.3 (1.8) ng/mL. Intrapatient CV was statistically higher (p = 0.00093) for MPA at 0.68 (0.29) when compared to Tac with a CV of 0.46 (0.12). CV did not correlate with eGFR. Intrapatient MPA trough level CV is significantly higher than for Tac, while CV for both MPA and Tac was high. MPA trough level monitoring may be a feasible monitoring option to improve patient exposure and possibly outcomes.

Progress in Pediatric Kidney Transplantation

This review summarizes the focus shift from ischemia-reperfusion injury and avoidance of rejection to long-term outcome after pediatric renal transplantation over the past decade. Although there has been excellent 1-year graft and patient survival, low rejection rates can be achieved with modern immunosuppression after pediatric renal transplantation, and patient survival is improved substantially in comparison with dialysis, pediatric renal transplant recipients experience a high prevalence of infections, malignancies, medication side effects, nonadherence, and, most importantly, cardiovascular morbidity and mortality. Additional challenges occur because of a high prevalence of obesity after transplantation and vascular calcifications. There is also in an underappreciation of chronic kidney disease (CKD) in transplant recipients. The etiology of CKD is multifactorial and can affect graft and patient survival. The rigors of treatment for CKD are less compared with CKD in nontransplant recipients. Almost all immunosuppressive drugs are implicated with a risk of hypertension, hyperlipidemia, and diabetogenicity, all of which contribute to cardiovascular morbidity. Corticosteroids exhibit the most substantial risk and also stunt growth. Effective new treatment protocols such as the recent European Tacrolimus and WIthdrawal of STeroids (TWIST) study with rapid steroid withdrawal after 5 days provide promising results without increasing the rejection risk. The shift in focus on long-term complications allows for improved graft outcome. Side effects of immunosuppressive medications require continued attention to further improve long-term outcomes.