Nathan W. Levin

Recognition and management of acute kidney injury in the International Society of Nephrology 0by25 Global Snapshot: a multinational cross-sectional study

BACKGROUND Epidemiological data for acute kidney injury are scarce, especially in low-income countries (LICs) and lower-middle-income countries (LMICs). We aimed to assess regional differences in acute kidney injury recognition, management, and outcomes. METHODS In this multinational cross-sectional study, 322 physicians from 289 centres in 72 countries collected prospective data for paediatric and adult patients with confirmed acute kidney injury in hospital and non-hospital settings who met criteria for acute kidney injury. Signs and symptoms at presentation, comorbidities, risk factors for acute kidney injury, and process-of-care data were obtained at the start of acute kidney injury, and need for dialysis, renal recovery, and mortality recorded at 7 days, and at hospital discharge or death, whichever came earlier. We classified countries into high-income countries (HICs), upper-middle-income countries (UMICs), and combined LICs and LMICs (LLMICs) according to their 2014 gross national income per person. FINDINGS Between Sept 29 and Dec 7, 2014, data were collected from 4018 patients. 2337 (58%) patients developed community-acquired acute kidney injury, with 889 (80%) of 1118 patients in LLMICs, 815 (51%) of 1594 in UMICs, and 663 (51%) of 1241 in HICs (for HICs vs UMICs p=0.33; p<0.0001 for all other comparisons). Hypotension (1615 [40%] patients) and dehydration (1536 [38%] patients) were the most common causes of acute kidney injury. Dehydration was the most frequent cause of acute kidney injury in LLMICs (526 [46%] of 1153 vs 518 [32%] of 1605 in UMICs vs 492 [39%] of 1260 in HICs) and hypotension in HICs (564 [45%] of 1260 vs 611 [38%%] of 1605 in UMICs vs 440 [38%] of 1153 LLMICs). Mortality at 7 days was 423 (11%) of 3855, and was higher in LLMICs (129 [12%] of 1076) than in HICs (125 [10%] of 1230) and UMICs (169 [11%] of 1549). INTERPRETATION We identified common aetiological factors across all countries, which might be amenable to a standardised approach for early recognition and treatment of acute kidney injury. Study limitations include a small number of patients from outpatient settings and LICs, potentially under-representing the true burden of acute kidney injury in these areas. Additional strategies are needed to raise awareness of acute kidney injury in community health-care settings, especially in LICs. FUNDING International Society of Nephrology.

A method for the estimation of hydration state during hemodialysis using a calf bioimpedance technique

Although many methods have been utilized to measure degrees of body hydration, and in particular to estimate normal hydration states (dry weight, DW) in hemodialysis (HD) patients, no accurate methods are currently available for clinical use. Biochemcial measurements are not sufficiently precise and vena cava diameter estimation is impractical. Several bioimpedance methods have been suggested to provide information to estimate clinical hydration and nutritional status, such as phase angle measurement and ratio of body fluid compartment volumes to body weight. In this study, we present a calf bioimpedance spectroscopy (cBIS) technique to monitor calf resistance and resistivity continuously during HD. Attainment of DW is defined by two criteria: (1) the primary criterion is flattening of the change in the resistance curve during dialysis so that at DW little further change is observed and (2) normalized resistivity is in the range of observation of healthy subjects. Twenty maintenance HD patients (12 M/8 F) were studied on 220 occasions. After three baseline (BL) measurements, with patients at their DW prescribed on clinical grounds (DW(Clin)), the target post-dialysis weight was gradually decreased in the course of several treatments until the two dry weight criteria outlined above were met (DW(cBIS)). Post-dialysis weight was reduced from 78.3 +/- 28 to 77.1 +/- 27 kg (p < 0.01), normalized resistivity increased from 17.9 +/- 3 to 19.1 +/- 2.3 x 10(-2) Omega m(3) kg(-1) (p < 0.01). The average coefficient of variation (CV) in three repeat measurements of DW(cBIS) was 0.3 +/- 0.2%. The results indicate that cBIS utilizing a dynamic technique continuously during dialysis is an accurate and precise approach to specific end points for the estimation of body hydration status. Since no current techniques have been developed to detect DW as precisely, it is suggested as a standard to be evaluated clinically.

Hemodialysis machines and monitors

The last decade has seen not only an enormous growth in the number of hemodialysis patients but also a concomitant growth in the number of hemodialysis machines produced every year by fewer companies than 10 years ago. Because the risk of accidents increases with the number of different machines in the field, standard organizations and government authorities worldwide have issued standards and laws that regulate the design of hemodialysis machines. Both effects have slowed the development of new concepts and the effective use of modern technology in hemodialysis machines. The extracorporeal circuit has remained unchanged for more than twenty years. Bicarbonate dialysis with single patient machines and volumetric ultrafiltration control which were developed in the late 70s took more than 10 years to be generally accepted. Cost pressure has been an effective driving force for the introduction of new technology. High-efficiency dialysis was introduced in order to reduce treatment time. Underdialysis of many patients was the result because in many cases the shortening of the treatment time was not sufficiently compensated for by the increased efficacy of the dialysis process

A Kinetic Model of Calcium Mass Balance during Dialysis Therapy

A kinetic model of Ca mass balance during dialysis has been developed. It is a single-compartment, variable-volume model to compute Ca mass balance during dialysis in its volume of distribution, the extracellular fluid. The model was used to analyze literature data which were suitable for the assessment of Ca mass balance over the course of dialysis. The modeled analyses predicted the serial plasma Ca concentrations very well. The mass balance analyses revealed a pool of rapidly diffusible Ca beyond the extracellular fluid distribution volume where Ca could be mobilized (M+Ca) or sequestered (M–Ca) very rapidly at rate equal but opposite in sign to dialyzer flux and thus effectively maintain near constant plasma Ca in the face of dialyzer Ca concentration gradients. This pool is likely the large pool of diffusible (miscible) Ca in connective tissue and on bone surfaces. Analysis of net Ca flux during dialysis with CdiCa = 2.50 mEq/l suggests that 80% of patients are in positive Ca balance during dialysis. Further studies are required to verify the model and to develop a model of interdialytic Ca mass balance.

Extracellular fluid redistribution during hemodialysis: bioimpedance measurement and model

Intradialytic fluid redistribution may cause hypotension. We hypothesized that measuring extracellular fluid volumes (ECV) with segmental bioimpedance analysis (SBIA) could test a simple, volume-driven model of redistribution among the arm, leg and trunk compartments. Patients (22, 5 females/17 males, with ages 60.2 +/- 9 years, weights 80.7 +/- 15 kg, heights 174 +/- 9 cm) were studied during 30 HD treatments on different days. Hypotensive symptoms (Hypo+) were observed in eight patients. ECVs in the arm, trunk and leg, respectively V(A), V(T) and V(L), were measured at initiation of, and throughout, dialysis. Two variables lambda(A) and lambda(L) were defined as V(A)/V(T) and V(L)/V(T). System dynamics, assuming initial equilibrium, are then described by two rate coefficients k(RL) and k(RA) and two constants beta and gamma. These were obtained using a Marquardt-Levenberg least-squares algorithm. Significant differences (Hypo+ versus Hypo-) for lambda(L) (0.55 +/- 0.13 versus 0.84 +/- 0.3, *p < 0.05) and lambda(A) (0.17 +/- 0.032 versus 0.23 +/- 0.07, **p < 0.01) were found. The small value of lambda(L) might indicate that less leg volume predisposes to hypotension, larger peripheral volume mitigates hypotension. Observed transport ratios indicated that the ratio of limb to trunk volume stabilized during dialysis after an initial adjustment. These data imply encumbered movement of water from the interstitial components around skeletal muscle in the arm and leg to those of the trunk and are useful in predicting anatomical or situational predispositions to hypotension.

Comparison of Outcomes on Continuous Ambulatory Peritoneal Dialysis Versus Automated Peritoneal Dialysis: Results from a USA Database

♦ Background and Objective: Automated peritoneal dialysis (APD) is being increasingly used as an alternative to continuous ambulatory peritoneal dialysis (CAPD). However, there has been concern regarding reduced sodium removal leading to hypertension and resulting in a faster decline in residual renal function (RRF). The objective of the present study was to compare patient and technique survival and other relevant parameters between patients treated with APD and patients treated with CAPD. ♦ Methods: Data for incident patients were retrieved from the database of the Renal Research Institute, New York. Treatment modality was defined 90 days after the start of dialysis treatment. In addition to technique and patient survival, RRF, blood pressure, and laboratory parameters were also compared. ♦ Results: 179 CAPD and 441 APD patients were studied. Mean as-treated survival was 1407 days [95% confidence interval (CI) 1211 – 1601] in CAPD patients and 1616 days (95% CI 1478 – 1764) in APD patients. Adjusted hazard ratio (HR) for mortality was 1.31 in CAPD compared to APD (95% CI 0.76 – 2.25, p = NS). Unadjusted as-treated technique survival was lower in CAPD compared to APD, with HR 2.84 (95% CI 1.65 – 4.88, p = 0.002); adjusted HR was 1.81 (95% CI 0.94 – 3.57, p = 0.08). Peritonitis rate was 0.3 episodes/patient-year for CAPD and APD; exit-site/tunnel infection rate was 0.1 and 0.3 episodes/patient-year for CAPD and APD respectively (p = NS). ♦ Conclusions: Patient survival was not significantly different between APD and CAPD patients, whereas technique survival appeared to be higher in APD patients and could not be explained by differences in infectious complications. No difference in blood pressure control or decline in RRF was observed between the 2 modalities. Based on these results, APD appears to be an acceptable alternative to CAPD, although technique prescription should always follow individual judgment.

Breath ethane in dialysis patients and control subjects.

Oxidant stress may play a role in the accelerated pathology of patients on dialysis, especially in the development of cardiovascular disease, which is a frequent condition in end-stage renal disease (ESRD) patients. Measurement of hydrocarbons can be employed to assess oxidant stress since breath hydrocarbons have been directly traced to in vivo breakdown of lipid hydroperoxides. We undertook to measure ethane, a major breath hydrocarbon, in 15 control subjects, 13 patients on peritoneal dialysis (PD), and 35 patients on hemodialysis (HD). Within the HD group, we separately examined 12 diabetic and 23 nondiabetic patients. Breath samples were collected after patients had breathed purified air for 4 min, and ethane content was measured by GC and expressed as pmoles/kg-body weight-minute (pmol/kg-min). As the data for the hemodialysis patients appeared skewed, nonparametric statistical techniques were employed to analyze these data, which are reported as median and interquartile range (IQR). Ethane levels were similar in 15 control subjects (median, 2.50 pmol [1.38-3.30]/kg-min] and 13 PD patients (median, 2.51 pmol [1.57-3.17]/kg-min). Breath ethane was significantly elevated in a portion (18 of 35 patients, 52%) of the HD patients (median, 6.16 pmol [4.46-8.88]/kg-min) (p <.001 vs. control, Mann-Whitney U test). Two of the diabetic HD patients showed extremely high values of breath ethane. Breath ethane was not altered by a single hemodialysis session, suggesting that long-term metabolic processes contribute to its elevation. Measurement of breath ethane may provide insight into severity of oxidant stress and metabolic disturbances, and provide guidance for optimal therapy and prevention of pathology in patients on long-term hemodialysis.

Application of Bioimpedance Techniques to Peritoneal Dialysis

Peritoneal dialysis (PD) has been used as a home dialysis therapy for renal replacement for more than 30 years. In a recent assessment of treatment quality, the mortality of patients on PD was referenced as being higher than of those on hemodialysis. Several reports suggest that a high proportion of PD patients are overhydrated. Clinical assessment of dry weight in PD patients is difficult and further complicated by the paucity of signs and symptoms indicative of dehydration (such as intradialytic hypotension or muscle cramps). Monitoring tools used for fluid status estimation during hemodialysis, e.g. online blood volume and blood pressure measurement, are not readily available in PD patients. Bioimpedance analysis technique has been considered as a potential tool to measure body fluid non-invasively, inexpensively and simply. Although Bioimpedance analysis has been used in clinical studies for more than 20 years, the knowledge of the electrical properties of body tissues is still evolving. In this review we aim to clarify the principles of different bioimpedance techniques and to introduce their applications in PD patients.

The Impact of Residual Renal Function on Hospitalization and Mortality in Incident Hemodialysis Patients

Background/Aims: Few data are available on the impact of residual renal function (RRF) on mortality and hospitalization in hemodialysis (HD) patients. The objective of our study was to compare clinical outcomes for HD patients with and without RRF. Methods: In a cohort of 118 incident HD patients with RRF (n = 51) and without RRF (n = 67) who started dialysis in a single center, we recorded demographics, laboratory data, medication, hospitalizations and mortality. Results: Patients without RRF were older (p = 0.007), had lower baseline serum albumin levels (p = 0.002) and spent 18.6 more days in hospital per year than those with RRF (p = 0.055). Mean survival time was significantly lower in patients without RRF (p = 0.027). In a Cox proportional hazards model, only RRF remained as a significant independent predictor. Conclusions: RRF is associated with significantly reduced mortality and hospital days, but does not decrease the hospitalization rate and time to first hospitalization.

Saliva urea dipstick test: application in chronic kidney disease.

BACKGROUND A noninvasive test for determining elevated levels of blood urea nitrogen (BUN) may be useful under circumstances in which there is limited access to laboratories. Because saliva urea nitrogen (SUN) parallels BUN, we investigated the diagnostic performance of a semiquantitative SUN dipstick to test for elevated BUN levels in patients with chronic kidney disease (CKD). MATERIALS AND METHODS Patients with CKD Stages 1 to 5D were studied. 50 µl of saliva were transferred onto the SUN test strip (Integrated Biomedical Technology, Elkhart, Indiana, IN, USA). SUN was determined after 1 minute by visual comparison of the color of the moistened test pad with 6 calibrated color blocks. Interobserver reproducibility was evaluated by independent observers, masked to urea concentrations of 6 calibrated urea solutions. Correlation between SUN and BUN was quantified by Spearmans rank correlation coefficient (RS), Kappa Statistic was employed to evaluate within-sample reproducibility of duplicates. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic performance of SUN. RESULTS 68 patients (31 females, 60 ± 14 years; 34 hemodialysis patients, 34 patients CKD Stages 1 - 4) were studied. Interobserver coefficient of variation was 4.9% at SUN levels > 50 mg/dl; within-sample reproducibility was 90%. SUN and BUN were correlated significantly (RS = 0.63; p < 0.01). Elevated BUN was diagnosed with high accuracy by SUN determination (area under the ROC curve: 0.90 (95% CI 0.85 - 0.95)). CONCLUSION Semiquantitative dipstick measurements of SUN can reliably identify CKD patients with elevated BUN levels.