Thomas A. Golper

Predialysis blood pressure and mortality risk in a national sample of maintenance hemodialysis patients

The role of predialysis blood pressure (BP) as a risk factor for the high mortality in chronic hemodialysis (HD) patients has remained controversial. The objective of the current study was to further explore in a national random sample of 4,499 US hemodialysis patients any relationship of systolic or diastolic and predialysis or postdialysis BP with mortality, while considering subgroups of patients and controlling for other patient characteristics and comorbidities. The main finding of this study is the association of a low predialysis systolic BP with an elevated adjusted mortality risk (relative mortality risk [RR] = 1.86 for systolic BP < 110, P < 0.0001). No association with an elevated mortality risk could be observed for predialysis systolic hypertension (RR = 0.98 to 0.99, not significant [NS]), except for an elevated risk of cerebrovascular deaths. Postdialysis systolic BP was associated with an elevated mortality risk both for low and high BP levels as compared with midrange BP. Further evaluation of the elevated mortality risk associated with low predialysis systolic BP indicated similar patterns for both diabetic and nondiabetic subgroups and for patients with and without congestive heart failure (CHF) or coronary artery disease, although it was more pronounced among those with CHF. The level of predialysis fluid excess did not modify these results substantially. The findings from this historical prospective national study do not argue against the treatment of hypertension and suggest greater attention to postdialysis hypertension. The strikingly elevated mortality risk with low predialysis systolic BP suggests that low predialysis BP needs to be viewed with great concern and avoided where possible.

Drug dosing consideration in patients with acute and chronic kidney disease—a clinical update from Kidney Disease: Improving Global Outcomes (KDIGO)

Drug dosage adjustment for patients with acute or chronic kidney disease is an accepted standard of practice. The challenge is how to accurately estimate a patients kidney function in both acute and chronic kidney disease and determine the influence of renal replacement therapies on drug disposition. Kidney Disease: Improving Global Outcomes (KDIGO) held a conference to investigate these issues and propose recommendations for practitioners, researchers, and those involved in the drug development and regulatory arenas. The conference attendees discussed the major challenges facing drug dosage adjustment for patients with kidney disease. In particular, although glomerular filtration rate is the metric used to guide dose adjustment, kidney disease does affect nonrenal clearances, and this is not adequately considered in most pharmacokinetic studies. There are also inadequate studies in patients receiving all forms of renal replacement therapy and in the pediatric population. The conference generated 37 recommendations for clinical practice, 32 recommendations for future research directions, and 24 recommendations for regulatory agencies (US Food and Drug Administration and European Medicines Agency) to enhance the quality of pharmacokinetic and pharmacodynamic information available to clinicians. The KDIGO Conference highlighted the gaps and focused on crafting paths to the future that will stimulate research and improve the global outcomes of patients with acute and chronic kidney disease.

Drug-induced acute kidney injury

Purpose of reviewThe purpose of this review is to describe the most prevalent mechanisms of drug-induced acute kidney injury, to define the risk factors for nephrotoxicity, and to analyze the available evidence for preventive measures. Recent findingsDrug toxicity remains an important cause of acute kidney injury that, in many circumstances, can be prevented or at least minimized by vigilance and early intervention. Recent studies have resulted in increased insight into the subcellular mechanisms of drug nephrotoxicity. Further improvement is to be expected from the identification of early markers of nephrotoxicity and an increasing involvement of a clinical pharmacist. SummaryThe main mechanisms of nephrotoxicity are vasoconstriction, altered intraglomerular hemodynamics, tubular cell toxicity, interstitial nephritis, crystal deposition, thrombotic microangiopathy, and osmotic nephrosis. Before prescribing a potentially nephrotoxic drug, the risk-to-benefit ratio and the availability of alternative drugs should be considered. Modifiable risk factors should be corrected. The correct drug dosage should be prescribed. Patients should be pre-hydrated and the glomerular filtration rate should be frequently monitored during the administration of a potentially nephrotoxic drug. Studies are needed to further elucidate the mechanisms of nephrotoxicity to design more-rational prevention and treatment strategies. Computer-based prescriber-order entry and an appropriately trained intensive care unit pharmacist are particularly helpful to minimize medication errors and adverse drug events.

Risk factors for peritonitis in long-term peritoneal dialysis: The Network 9 peritonitis and catheter survival studies

To determine factors involved in peritoneal dialysis-associated peritonitis and catheter loss, all point prevalent peritoneal dialysis patients in Health Care Finance Administration (HCFA) end-stage renal disease (ESRD) Network 9 were followed throughout 1991 for peritonitis events and throughout 1991 to 1992 for catheter survival. Data were collected by questionnaires compiled by the dialysis facility and validated by network staff. Peritonitis was reported 1,168 times in 729 of the 1,930 patients. By gamma-Poisson regression, a significantly increased risk for peritonitis was observed for patients with previous peritonitis, black race, and those dialyzing with standard connectors or cyclers compared with disconnect systems. Decreased risks were observed for patients with longer ESRD experience and when prophylactic antibiotics were administered before catheter insertion. Postinsertion leakage, diabetes, visual problems, previous or current immunosuppression, and physical activity were not risk factors. Infection of any kind caused the removal of 68% of the 414 catheters lost. Patients with downward-directed tunnels were less likely to experience concomitant exit site/tunnel infections associated with peritonitis. Peritonitis episodes with Staphylococcus epidermidis-like organisms were more likely to resolve with a single course of antibiotics. Perhaps because of their higher infection rate, blacks were more likely than whites to use a disconnect system. In general, the outcome of peritonitis in blacks was similar to that in whites, except that blacks were less likely to be hospitalized and were less likely to die.

Continuous Arteriovenous Hemofiltration in Acute Renal Failure

This extensive review describes the settings for continuous arteriovenous hemofiltration (CAVH) and attempts to compare it to traditional dialysis therapies for acute renal failure. In addition hemodynamic stability, membrane biocompatibility, nutrition, fluid and solute removal, operational characteristics, anticoagulation, replacement solutions, drug removal, complications, and trouble shooting during CAVH are all discussed in detail. The cost of CAVH v dialysis is equal. CAVH is probably the renal replacement therapy of choice for hemodynamically unstable patients with acute renal failure and contraindications to peritoneal dialysis.

Reduction of cyst volume for symptomatic management of autosomal dominant polycystic kidney disease.

A total of 11 patients with refractory pain secondary to autosomal dominant polycystic kidney disease underwent ultrasound guided percutaneous aspiration of cyst fluid on the affected side. Surgical reduction of cyst volume was performed if pain recurred. Dramatic relief of pain was observed after both procedures. The probability of a patient being free of renal pain at 18 months was 33 +/- 17 per cent for aspiration and 81 +/- 12 per cent for an operation. Individual patients had relief of pain for more than 4 years. There was no deleterious effect on renal function after either aspiration or an operation. Blood pressure improved in the 5 patients with hypertension. There were no complications of percutaneous cyst aspiration. One patient required neurolysis of the drain site after cyst reduction.

Guidelines for Drug Therapy in Renal Failure

Five tables are presented that provide guidelines for drug usage in patients with renal insufficiency. The data are derived from the current medical literature. If specific information about a drug is unavailable, emphasis is given to normal pharmacokinetic variables in arriving at recommendations for therapy. Nephrotoxicity of adverse effects in patients with renal disease are noted and adjustments for dialysis suggested.

Vancomycin pharmacokinetics, renal handling, and nonrenal clearances in normal human subjects

The renal handling of vancomycin is unknown. Previously reported studies have not achieved steady‐state conditions with constant vancomycin concentrations. We measured systemic vancomycin clearance simultaneously with the renal clearances of vancomycin, creatinine, inulin, and para‐aminohippurate in nine healthy subjects at steady‐state serum vancomycin concentrations of 7 and 14 mg/L. For all steady‐state observations the renal clearance of vancomycin was 89 ± 11 ml/min (mean ± SE), the clearance of inulin 105 ± 9 ml/min, the clearance of creatinine 117 ± 9 ml/min, and the clearance of para‐aminohippuric acid 496 ±41 ml/min. The systemic clearance of vancomycin was 131 ± 7 ml/min. The clearances of creatinine, inulin, and para‐aminohippuric acid and the renal clearance of vancomycin were not statistically different at both steady‐state vancomycin concentrations. The ratio of the renal clearance of vancomycin to the clearance of inulin was 0.89 ± 0.06 and to creatinine clearance 0.79 ± 0.05. Both ratios were independent of vancomycin concentration, urine flow rate, and filtration fraction. The systemic clearance of vancomycin was 10% greater at serum vancomycin concentrations of 14 mg/L than at 7 mg/L (p < 0.05) because of an increase in the nonrenal clearance. Therefore in healthy subjects, 30% of the systemic vancomycin clearance is by nonrenal mechanisms and this nonrenal clearance is concentration dependent. Assuming protein binding to be between 10% and 20%, renal vancomycin excretion is predominantly by glomerular filtration. Small amounts of tubular vancomycin transport cannot be excluded by these techniques.

Twice-Weekly and Incremental Hemodialysis Treatment for Initiation of Kidney Replacement Therapy

Mortality is highest in the first months of maintenance hemodialysis (HD) therapy. In many Western countries, patients who transition to kidney replacement therapy usually begin thrice-weekly HD regardless of their level of residual kidney function (RKF). RKF is a major predictor of survival. RKF may decline more rapidly with thrice-weekly HD treatments, is associated with a reduced need for dialytic solute clearance, and is an important factor in the prescription of peritoneal dialysis. In this article, we review the concept of incremental HD, in which weekly dialysis dose, in particular HD treatment frequency, is based on a variety of clinical factors, such as RKF (including urine output > 0.5 L/d), volume status, cardiovascular symptoms, body size, potassium and phosphorus levels, nutritional status, hemoglobin level, comorbid conditions, hospitalizations, and health-related quality of life. These 10 clinical criteria may identify which patients might benefit from beginning maintenance HD therapy twice weekly. Periodic monitoring of these criteria will determine the timing for increasing dialysis dose and frequency. We recognize that twice-weekly HD represents a major paradigm shift for many clinicians and jurisdictions. Therefore, we propose conducting randomized controlled trials of twice-weekly versus thrice-weekly HD to assess the potential of twice-weekly HD to improve survival and health-related quality of life while simultaneously reducing costs, protecting fragile vascular accesses, and optimizing resource use during the first year of hemodialysis therapy. Such incremental and individualized HD therapy may prove to be the most appropriate approach for transitioning to dialytic therapy.

Technical Breakthroughs in the Wearable Artificial Kidney (WAK)

BACKGROUND The wearable artificial kidney (WAK) has been a holy grail in kidney failure for decades. Described herein are the breakthroughs that made possible the creation of the WAK V1.0 and its advanced versions V 1.1 and 1.2. DESIGN The battery-powered WAK pump has a double channel pulsatile counter phase flow. This study clarifies the role of pulsatile blood and dialysate flow, a high-flux membrane with a larger surface area, and the optimization of the dialysate pH. Flows and clearances from the WAK pump were compared with conventional pumps and with gravity steady flow. RESULTS Raising dialysate pH to 7.4 increased adsorption of ammonia. Clearances were higher with pulsatile flow as compared with steady flow. The light WAK pump, geometrically suitable for wearability, delivered the same clearances as larger and heavier pumps that cannot be battery operated. Beta(2) microglobulin (beta(2)M) was removed from human blood in vitro. Activated charcoal adsorbed most beta(2)M in the dialysate. The WAK V1.0 delivered an effective creatinine clearance of 18.5 +/- 3.2 ml/min and the WAK V1.1 27.0 +/- 4.0 ml/min in uremic pigs. CONCLUSIONS Half-cycle differences between blood and dialysate, alternating transmembrane pressures (TMP), higher amplitude pulsations, and a push-pull flow increased convective transport. This creates a yet undescribed type of hemodiafiltration. Further improvements were achieved with a larger surface area high-flux dialyzer and a higher dialysate pH. The data suggest that the WAK might be an efficient way of providing daily dialysis and optimizing end stage renal disease (ESRD) treatment.