Gaurang M. Shah

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.

Residual Kidney Function Decline and Mortality in Incident Hemodialysis Patients

In patients with ESRD, residual kidney function (RKF) contributes to achievement of adequate solute clearance. However, few studies have examined RKF in patients on hemodialysis. In a longitudinal cohort of 6538 patients who started maintenance hemodialysis over a 4-year period (January 2007 through December 2010) and had available renal urea clearance (CLurea) data at baseline and 1 year after hemodialysis initiation, we examined the association of annual change in renal CLurea rate with subsequent survival. The median (interquartile range) baseline value and mean±SD annual change of CLurea were 3.3 (1.9-5.0) and -1.1±2.8 ml/min per 1.73 m2, respectively. Greater CLurea rate 1 year after hemodialysis initiation associated with better survival. Furthermore, we found a gradient association between loss of RKF and all-cause mortality: changes in CLurea rate of -6.0 and +3.0 ml/min per 1.73 m2 per year associated with case mix-adjusted hazard ratios (95% confidence intervals) of 2.00 (1.55 to 2.59) and 0. 61 (0.50 to 0.74), respectively (reference: -1.5 ml/min per 1.73 m2 per year). These associations remained robust against adjustment for laboratory variables and ultrafiltration rate and were consistent across strata of baseline CLurea, age, sex, race, diabetes status, presence of congestive heart failure, and hemoglobin, serum albumin, and serum phosphorus levels. Sensitivity analyses using urine volume as another index of RKF yielded consistent associations. In conclusion, RKF decline during the first year of dialysis has a graded association with all-cause mortality among incident hemodialysis patients. The clinical benefits of RKF preservation strategies on mortality should be determined.

Ascorbic acid supplements in patients receiving chronic peritoneal dialysis.

Ascorbic acid supplements are commonly prescribed to patients with end-stage renal disease receiving peritoneal dialysis. To establish the need for ascorbic acid supplements, we evaluated seven chronic peritoneal dialysis patients during a supplement-free (phase I) period, and while receiving oral ascorbic acid (0.57 mmol/d [100 mg/d]) (phase II). Because of a proposed interaction with vitamin B6, patients were additionally supplemented with pyridoxine HCl (59.6 mumol/d [10 mg/d]) (phase III). Plasma levels and dialysate removal rates of total ascorbic acid and plasma pyridoxal-5-phosphate (PLP) were measured at the end of each phase. During phase I, plasma ascorbic acid levels (normal, 45 to 57 mumol/L [0.8 to 1.0 mg/dL]) declined slightly from 74 +/- 11 mumol/L (1.3 +/- 0.2 mg/dL) to 62 +/- 11 mumol/L (1.1 +/- 0.2 mg/dL) (P less than 0.02) at the end of the third week, and then remained stable to the end of the fourth week. Plasma ascorbic acid levels were no different in patients with or without residual renal function. With the addition of vitamin C supplements, plasma ascorbic acid levels increased by 45% of the baseline value at the end of phases II (P less than 0.001). The dialysate removal rate of ascorbic acid was 0.28 +/- 0.03 mmol/d (50 +/- 6 mg/d) at the end of phase I, and increased by 57% of the baseline value at the end of phases II (P less than 0.001). However, the peritoneal clearance of ascorbic acid remained unchanged during all phases the study. Pyridoxine depletion or repletion had no effect on plasma ascorbic acid levels (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of a Magnesium-Free Dialysate on Magnesium Metabolism During Continuous Ambulatory Peritoneal Dialysis

While the use of magnesium-containing compounds is usually contraindicated in dialysis patients, the risk of toxicity from hypermagnesemia can be reduced by lowering the magnesium concentration in dialysate. We examined the effects of a magnesium-free dialysate on both serum magnesium level and the peritoneal removal rate of magnesium over 12 weeks in 25 stable patients undergoing continuous ambulatory peritoneal dialysis (CAPD). After 2 weeks, the serum magnesium level decreased from 2.2 to 1.9 mg/dL (0.9 to 0.8 mmol/L) (P less than .02) and the peritoneal removal rate increased from 66 to 83 mg/d (2.8 to 3.5 mmol/d) (P less than .05), with both values remaining stable thereafter. There was a strong association between these parameters (r = -0.62, P less than .05), suggesting that the serum magnesium level decreased as a result of the initial increased peritoneal removal rate. For an additional 4-week period, a subgroup of nine patients received magnesium-containing, phosphate binding agents instead of those containing only aluminum. During this phase, serum inorganic phosphorus was well controlled. The serum magnesium level increased only from 1.8 to 2.5 mg/dL (0.7 to 1.0 mmol/L) (P less than .05), due in great part to the concomitant 41% rise in peritoneal magnesium removal from 91 to 128 mg/d (3.8 to 5.3 mmol/d) (P less than .05). No toxicity was noted during the entire 16-week study period, nor did serum calcium change. Thus, serum magnesium levels remained within an acceptable range as magnesium-containing phosphate binders were given through the use of magnesium-free peritoneal dialysate.(ABSTRACT TRUNCATED AT 250 WORDS)

Peritoneal catheters: a comparative study of column disc and Tenckhoff catheters.

A functioning peritoneal access is crucial to the success of peritoneal dialysis. We report retrospective analysis of our experience using 44 Tenckhoff and 23 column disc, double-cuff, catheters in 46 patients receiving peritoneal dialysis. Postoperative care was identical in both groups. Both catheter groups were comparable with regards to age, sex, obesity and prior abdominal surgery. Catheter removal due to drainage failure was significantly greater with the column disc than the Tenckhoff catheters (22% vs 5%, p = 0.04). In addition, 39% of column disc catheters compared to 11% Tenckhoff catheters were removed as a result of therapy resistant peritonitis (p = 0.011). Furthermore, there was a greater incidence of peritonitis with the column disc than with the Tenckhoff catheters at the end of the first year (71% vs 42%, p < 0.01). There was no difference between the two groups with respect to other complications, such as pericatheter leak, catheter infections, catheter cuff-extrusion or hernia. Our experience indicates that the column disc catheter is associated with higher complication rates and does not offer any advantage over the Tenckhoff catheter

Verapamil Kinetics during Maintenance Hemodialysis

The kinetics of verapamil during chronic oral therapy were evaluated in a maintenance hemodialysis patient. The elimination half-lives of verapamil and its major metabolite norverapamil were 3.8 and 15.2 h. The former is shorter, while the latter is similar to that in patients with normal renal function. Hemodialysis did not affect drug half-life, and neither drug could be detected in the dialysate. Our studies suggest that verapamil kinetics are altered in end-stage renal disease and that hemodialysis does not remove significant amounts of the drug or its metabolite.

Thrombotic microangiopathy and human immunodeficiency virus in the era of eculizumab

Thrombotic microangiopathies (TMAs) include thrombotic thromobocytopenic purpura and hemolytic uremic syndrome (HUS). Among these conditions, atypical HUS is now recognized to be a disease of alternative complement pathway dysregulation. Eculizumab is a recombinant humanized monoclonal antibody that binds to the complement protein C5 and prevents the cleavage of C5 to C5a and C5b. Eculizumab has been used as a novel treatment for complement-mediated TMA. We present a case of a patient with human immunodeficiency virus infection who developed TMA and was successfully treated with eculizumab. The effect of long-term treatment with this new medication is unknown, and further studies are needed to establish guidelines in the management of this condition.

Acyclovir Pharmacokinetics in a Patient on Continuous Ambulatory Peritoneal Dialysis

Acyclovir is an effective agent for the treatment of herpes virus infections, however, the pharmacokinetics of the drug are altered in renal failure. We studied this drug in a continuous ambulatory peritoneal dialysis (CAPD) patient who was immunocompromised and had cutaneous herpes infection. The elimination half-life (17.1 hours) was similar to that reported for end-stage renal disease (ESRD) patients, while the volume of the central compartment (29.6 L/1.73 m2), the steady state volume of distribution (68.1 L/1.73 m2), and the total body clearance (48.3 mL/min/1.73 m2) were greater. The mean CAPD clearance was only 4.4 mL/min, with less than 10% of an administered dose being recovered in the 24-hour dialysate. Further studies are needed to establish a dosing regimen for CAPD patients.

Elevated plasma lipoprotein(a) levels and hypoalbuminemia in peritoneal dialysis patients.

Plasma lipoprotein(a), Lp(a), is strongly and independently associated with atherosclerosis, and levels are elevated in hemodialysis (HD) patients and in some studies of those on peritoneal dialysis (PD). We hypothesized that protein losses and hypoalbuminemia could stimulate hepatic Lp(a) synthesis, and this effect would be accentuated in PD patients with malnutrition. The PD subjects (n=24) had higher plasma Lp(a) levels than those (n=10) on HD (median 34.4 vs 21.0 mg/dl, p<0.05), and values exceed normal in 62.5% vs 20% of the subjects (p<0.03), respectively. The serum albumin levels inversely correlated with concentrations of Lp(a) and apolipoprotein B, as well as the apolipoprotein B/AI ratio. In conclusion, plasma Lp(a) concentrations are frequently elevated in PD as well as HD patients. Measuring Lp(a) levels is useful in identifying patients at increased atherogenic risk, which may not be reflected in routine lipid profiles. The negative correlation between plasma Lp(a) and albumin levels suggests that the latter may be linked pathophysiologically to hepatic Lp(a) production. The association of hypoalbuminemia with higher Lp(a) values is of particular concern because malnutrition frequently occurs in PD patients.

Peritoneal leucocyte response to bacterial peritonitis in patients receiving peritoneal dialysis.

We evaluated the quantitative peritoneal leucocyte response to antibiotic therapy in 25 CAPD patients with 57 episodes of bacterial peritonitis. Eighty-eight percent of the peritonitis episodes were initially treated with a first generation cephalosporin, but results of microbial sensitivity studies led to a change in the initial antibiotic regimen in 23 episodes. Overall, 47/57 (82%) episodes were cured by antibiotic therapy alone (responders), while 10/57 (18%) required removal of the peritoneal catheter as a curative procedure (nonresponder). Neither the duration of symptoms on initial presentation nor the status of being a nonresponder could be related to the baseline peritoneal leucocyte values, either the total (PLC) or polymorphonuclear counts (PMN). Since the baseline PLC and PMN showed a 500-fold variation, subsequent changes were expressed as a percent [PLC (%) and PMN-PLC (%)] of the baseline value. On day 3 of peritonitis, PLC (%) and PMN-PLC (%) were less in responders (26% and 10%) than nonresponders (251% and 254%) (p<0.001). Differentiation between responders and nonresponders based on PLC (%) and PMN-PLC (%) was associated with a high degreee of sensitivity (90%) and specificity (90%). Similar results were obtained for day 4. These data suggest that the temporal pattern of PLC and PMN, when expressed as a percentage of the baseline value, may be useful in predicting those episodes of peritonitis which require removal of the peritoneal catheter.