Michael J. Flanigan

Dialysate sodium delivery can alter chronic blood pressure management

Low dialysate sodium concentrations can reduce postdialysis thirst and serum sodium activity, but patients typically experience dialysis hypotension, fatigue, disequilibrium, and cramps. High-sodium hemodialysis minimizes dialysis disequilibrium but increases the serum sodium activity of most patients. Programmed variable-sodium dialysis can minimize dialysis discomfort but may also alter the sodium kinetics from those of high-sodium dialysis. We designed a cross-over study with random order assignment to determine whether a variable-sodium dialysis program could reduce the blood pressure of dialysis patients without increasing dialysis morbidity. Dialysis with a dialysate sodium of 140 mEq/L was compared with dialysis with a programmed exponential decrease of dialysate sodium from 155 mEq/L to 135 mEq/L. Dialysate sodium was then held constant at 135 mEq/L for the final half hour of dialysis. Eighteen patients completed the 7-month study, each receiving 3.5 months of experimental and 3.5 months of standard therapy. Programmed variable-sodium dialysis resulted in a reduction in antihypertensive drug use without alterations in predialysis blood pressure, interdialytic weight gain, ultrafiltration tolerance, or the frequency of symptomatic dialysis cramps or hypotension. Patients did, however, have lower postdialysis standing blood pressures and higher postdialysis target weights during programmed variable-sodium dialysis.

Reducing the Hemorrhagic Complications of Hemodialysis: A Controlled Comparison of Low-Dose Heparin and Citrate Anticoagulation

We report a randomized prospective study comparing the results of anticoagulation using hypertonic trisodium citrate and low-dose controlled heparin during 45 hemodialysis treatments performed on patients determined to be at high or very high risk for bleeding. Dialysis-associated bleeding was more frequent following low-dose controlled heparin anticoagulation than during hypertonic citrate therapy (P less than .05). Dialysis effectiveness measured by postdialysis chemistries and weight loss was equivalent in the two groups.

Cellular Response to Peritonitis Among Peritoneal Dialysis Patients

White blood cell counts and differential cell counts were performed on 249 peritoneal dialysis effluents from 48 patients using chronic peritoneal dialysis. The finding of more than 50% polymorphonuclear leukocytes in the dialysate was a more sensitive indicator of peritonitis than was an absolute cell count of 100 cells/microL. This finding was true for patients using intermittent peritoneal dialysis, continuous ambulatory peritoneal dialysis, and continuous cycling peritoneal dialysis.

HYPERTENSION IN HEMODIALYSIS PATIENTS: Dialysate Composition and Hemodialysis Hypertension

Dialysis prescriptions have evolved to take advantage of new technology and serve a burgeoning patient population. High‐sodium bicarbonate‐based dialysate was first formulated in 1982 to enable short, safe, comfortable, high‐efficiency hemodialysis (HD). Near‐universal adaptation of these high‐sodium formulas has virtually eliminated profound dialysis disequilibrium and greatly reduced dialysis discomfort, but has created a syndrome of dialysis salt loading with accentuated postdialysis thirst, interdialytic weight gain, and hypertension. Available technology will soon permit individuals to receive isonatremic dialysis with dialysate customized to the patients serum sodium activity. Then, rather than choosing between comfortable, safe, high‐efficiency dialysis with salt loading; cramps, asthenia, and symptomatic hypotension using low‐sodium, high‐efficiency rapid HD to control blood pressure (BP) and weight gain; or comfortable, slow, low‐efficiency HD with BP control, physicians may be able to minimize symptoms and avoid dialysis salt loading while providing maximum time for rehabilitative activities. The current use of a single sodium activity for all patients ignores the inter‐ and intraindividual variability in serum sodium activity in our patients. This results in undesired consequences for 20–40% of patients. The application of even more severe salt loading through high‐salt sodium modeling only accentuates the long‐term problems of excessive thirst, weight gain, and hypertension.

Quantitating Hemodialysis: A Comparison of Three Kinetic Models

Three urea kinetic analyses were applied to hemodialysis and their conformity assessed. Sixteen patients underwent 50 measurements of dialyzer clearance (K), protein catabolic rate (PCR), and dialysis quantification (Kt/V) using the urea kinetic model (UKM) of Gotch and Sargent, Malcheskys direct dialysis quantification (DDQ), and the graphic technique of urea reduction analysis (URA) devised by Keshaviah. Additionally, the equations proposed by Jindal (percent urea reduction), and Daugirdas were used to calculate Kt/V values for each study. Dialyzer performance determined by whole blood urea clearance consistently exceeded simultaneous dialysate urea removal and was 55% greater than the clearance calculated by DDQ. Despite these variations, dialysis adequacy (Kt/V) and normalized protein catabolic rate (nPCR) were remarkably constant when derived by fixed-volume single-pool analyses (ie, UKM, DDQ, and URA). Application of variable-volume corrections increased Kt/V and nPCR, but caused DDQ values to diverge from those of UKM and URA. During rapid high-efficiency dialysis (RHED), the UKM predicted urea removal in excess of that documented by DDQ. During this trial (low-level RHED with K = 2.98 mL.kg-1 per min), urea dysequilibrium across blood-cell interfaces was sufficient to cause UKM to overestimate protein catabolism by 5%. The basic assumption of single-pool kinetics may be inappropriate during RHED, and further increases in dialyzer clearance will increase the discrepancy between projected and actual urea removal. Future comparisons of RHED prescriptions should employ mass balance data, or redesigned kinetic analyses.

Tidal Peritoneal Dialysis: Kinetics and Protein Balance

Some patients find automated peritoneal dialysis preferable to continuous ambulatory peritoneal dialysis (CAPD). Unfortunately, automated peritoneal dialysis prescriptions are time consuming and can impede rehabilitation. We wished to determine whether an 8-hour tidal peritoneal dialysis (TPD) prescription could maintain the time averaged blood urea nitrogen at 60 mg/dL or less while patients consumed a diet containing approximately 1.2 g protein/kg body weight/d. Ten home dialysis patients previously stabilized on continuous cyclic peritoneal dialysis volunteered for a metabolic balance study conducted at the University of Iowas Clinical Research Center. A peritoneal equilibration test was conducted and mass transfer area coefficients (MTaCs) were derived for each subject. Nitrogen balance was measured during the last 5 days of a 12-day constant diet while patients underwent a series of monitored nocturnal dialyses. Mass transfer area coefficient measurements were reproducible and independent of the filling volume and ultrafiltration, but varied between subjects (normalized MTaCurea = 33.6 +/- 16.3 mL/min, normalized MTaCcrt = 16.3 +/- 9.5 mL/min). Tidal peritoneal dialysis urea and creatinine clearances could be predicted by these MTaC values (r2 = 0.70 urea, r2 = 0.91 creatinine). Nitrogen balance assumptions predicted, and we confirmed, a relationship between dietary protein intake and urea nitrogen generation (r2 = 0.82) during TPD. A normalized protein catabolic rate of 1.2 g/kg/d resulted in a urea nitrogen generation rate of approximately 100 mg/kg/d. If a patients protein intake was approximately 1.2 g/kg/d, then TPD with a weekly urea clearance normalized to body volume (Kt/V(urea)) of approximately 2.1 (urea clearance, approximately 0.35 mL/kg/min) could maintain a time averaged blood urea nitrogen of approximately 60 mg/dL.(ABSTRACT TRUNCATED AT 250 WORDS)

The Significance of Protein Intake and Catabolism

Diet and nutrition are integral to the management of individuals with renal disease. Uremia engenders anorexia, nausea, meat aversion, and emesis, disturbances that ultimately reduce appetite and cause weight loss and malnutrition. Protein restriction can alleviate these uremic symptoms and improve patient health and vigor, but overly zealous protein restriction may, itself, produce malnutrition. This is particularly likely when energy intake is restricted by either design or anorexia. End-stage renal disease patients require renal replacement therapy for survival, and although dialysis is life sustaining, it neither replaces normal kidney function nor obviates the need for dietary management. In this setting of controlled, persistent uremia, undernutrition can develop surreptitiously. Dialysis physicians have long regarded malnutrition as a sign of uncontrolled uremia and failing health. This supposition has now been validated by epidemiologic studies demonstrating that serum albumin and protein catabolic rate (PCR) discriminate between dialysis patients at high and low risk of death or illness. This correlation of undernutrition with health and survival persists across wide ranges of age, medical diagnoses, and dialysis prescriptions. Because PCR is readily measured using urea kinetic analyses, it has been promoted as a patient monitoring tool and under steady-state conditions it is a reliable method of determining protein intake. Although a single PCR measurement does not integrate day-to-day dietary and metabolic fluctuations and contains an inherent uncertainty of +/- 20%, sequential measurements can be used to assess changes in an individuals dietary protein intake. PCR defines nitrogen losses and, when normalized to a realistic index of metabolic activity (metabolically active body size), it can disclose subtle individual variances in nitrogen utilization. These normalized protein catabolic rates (NPCR) do not, however, measure or describe overall nutrition. The normalization schemes employed are based on population averages and only approximate an individuals true metabolic activity. Thus, using NPCR to define nutritional needs can result in overfeeding obese and underfeeding wasted subjects. Instead, nutritional adequacy should be defined by clinical inspection and comparison with defined standards. Once that state is defined, and desirable protein and calorie intakes are determined, NPCR can be used to monitor the patients ability to maintain homeostasis.

Organ and Metabolic Complications — Abnormal Endocrine Function in Chronic Renal Failure

Endocrine function is often abnormal in patients with chronic renal failure (CRF); these disturbances, though not life-threatening, diminish the quality of life and make interpretation of endocrine function tests difficult. The pathogenesis of these derangements are multi-factorial and complex in nature and can be classified as follows: n n n- Hormonal deficiency due to the absence of functioning renal mass — erythropoietin, 1,25 vitamin D3, renin and osteogenic or bone morphogenic protein, a bone growth promoting factor (1) n n n- Hormonal deficiency due to uremia — Testosterone n n n- Hormonal excess due to increased production — Parathyroid hormone (PTH), prolactin and growth hormone (GH) n n n- Hormonal excess due to decreased degradation — GH, prolactin, insulin and glucagon n n n- Altered feedback regulation — gonadal dysfunction and excess GH and prolactin production n n n- Altered hormone metabolism — impaired conversion of thyroxine to triiodothyronine n n n- Altered end organ responsiveness — insulin and PTH resistance

Report & Commentary: The NKF-DOQI Anemia Guidelines: Not Appropriate as Performance Measures for Peritoneal Dialysis

The Health Care Financing Administration (HCFA) has enacted significant changes to the Medicare and Medicaid Programs (1). Among these has been the formation of a Health Care Quality Improvement Program (HCQIP) which, in conjunction with the End Stage Renal Disease (ESRD) Networks, initiated the ESRD Core Indicators Project to demonstrate that the health care provided to ESRD beneficiaries could be measurably improved. This project was based on the premise that ESRD Networks might do more to improve quality and cost-effectiveness by bringing typical management into line with “best practices” rather than by inspecting individual cases to identify erred treatment. This statistical approach toward outcomes-based quality improvement is now evolving into a performance measures program. Quality improvement initiatives are intended to improve medical care. The National Kidney Foundation– Dialysis Outcomes Quality Initiatives (DOQITM) identify key areas of patient management and provide practice guidelines intended to affect survival, health, and cost of care. These guidelines describe desirable outcomes and are meant to “assist practitioner and patient decisions about appropriate heath care for specific circumstances” and “facilitate continuous improvement . . . as new information becomes available” (2). Performance measures are tools that permit consumers and purchasers to compare the value of health services provided by competing delivery systems (3). HCFA implemented the ESRD Core Indicators Project as a statistical sampling quality-of-care initiative to improve health care by establishing outcome priorities. HCFA now intends to authorize performance standards and provide incentives for providers to comply with these measures. Through performance measures, “consumers will be able to choose among health plans and providers based on their relative value and quality . . . and HCFA will make qualityoriented payment and coverage policy decisions based on the best evidence available” (1). The ESRD Core Indicators Project is intended to evolve into a performance measures program, the measures to be chosen from the DOQI guidelines (4). Not all practice guidelines can appropriately be converted into performance indicators or measurement tools permitting purchasers to compare the value of health services provided by competing delivery systems (5). The 1998 Core Indicators Report on Anemia in Peritoneal Dialysis uggests that applying DOQI anemia management principles to peritoneal dialysis (PD) may represent such an instance. There is rigorous evidence that anemia impairs uremic individuals, that recombinant human erythropoietin (r-HuEPO) can ameliorate uremic anemia, and that using r-HuEPO to ameliorate anemia enhances the health and well-being of dialysis patients (6). The actual hematocrit range to be obtained and the process by which this outcome is achieved appear to be less assured. DOQI guidelines deem the desired hematocrit range for erythropoietin-treated patients to be between 33% and 36%. The 1998 Peritoneal Dialysis–Core Indicators Study report discloses that whereas 59% of r-HuEPOtreated PD patients have a hematocrit in excess of 33%, only 36% achieve the DOQI goal because 23% of patients have a hematocrit of more than 36%. Among healthy adults, the standard deviation for hematocrit measured by an automated system is ± 6% (7). Using similar methodology, the variability (± 1 SD) of the PD population is ± 4%, and the distribution pattern approximates a normal distribution, with physicians aiming for a mean hematocrit value of approximately 34%. In this population, 60% of patients have a hematocrit between 30% and 36%, whereas 23% have a hematocrit in excess of 36%. If the DOQI recommendation that hematocrits be maintained between 33% and 36% is taken literally, then clinicians would attempt to achieve a mean hematocrit of 34.5%. Unless the population standard deviation can be reduced to less than ± 4%, such an effort will predictably result in at least 30% of patients having a hematocrit in excess of 36%, a value not justified by the DOQI anemia work group nor desired by third-party payers. The hematocrit of a healthy individual has diurnal variability, with a ± 3.7% coefficient of variation (8), and the automated measurement system used at University of Iowa Hospitals and Clinics Clinical Laboratory has a coefficient of variation of ± 2.7%. The combined methodologic and biological variations yield an expected measurement variability (standard deviation) of ± 2% for a hematocrit of 34.5%. This implies that if all PD paAddress correspondence to: Michael J. Flanigan, MD, Department of Medicine, T-305-GH, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242-4060. E-mail: mjf@inav.net. Seminars in Dialysis—Vol 12, No 3 (May–June) 1999 pp. 162–163

Report & Commentary: 1998 Core Indicators Study—Anemia in Peritoneal Dialysis: Implications for Future Monitoring

Michael J. Flanigan, Michael V. Rocco, and Diane Frankenfield Department of Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa (MJF); Wake Forest University School of Medicine, Wake Forest University, Winston-Salem, North Carolina (MVR); and the Quality Measurement and Health Assessment Group, Office of Clinical Standards and Quality, Health Care Financing Administration, Baltimore, Maryland (DF)