Carl M. Kjellstrand

Sodium ramping in hemodialysis: A study of beneficial and adverse effects

Sodium ramping has been introduced as a technique to decrease side effects occurring during hemodialysis. We studied sodium ramping in 414 dialysis sessions in 23 patients by randomizing 2-week blocks of dialysis to either steady dialysate sodium of 140 mEq/L, linear sodium ramping during dialysis from 155 mEq/L to 140 mEq/ L, or stepwise ramping (sodium of 155 mEq/L for 3 hours and 140 mEq/L for 1 hour). We studied the number and severity of hypotensive and hypertensive episodes. A hypotensive episode was defined as an abrupt decline of systolic blood pressure of more than 50 mm Hg, a decrease in blood pressure accompanied by symptoms requiring intervention, or systolic blood pressure of less than 90 mm Hg even without symptoms. A hypertensive episode was defined as a sudden increase in systolic blood pressure of over 30 mm Hg. We also recorded other side effects (headache, cramps, nausea, vomiting, dizziness, thirst, fatigue, weight gain, and blood pressure) during, immediately after, and between dialysis sessions. There was no major difference between the two ramping protocols, but compared with standard dialysis, both decreased total number of side effects from 4.0 to 3.0 (P = 0.057); the number of hypotensive episodes decreased from 1.3 to 0.7 (P = 0.036). The lowest blood pressure was 114/66 mm Hg during control and 123/69 mm Hg during ramping (P < 0.0001). The frequency of cramps during dialysis decreased from 0.9 to 0.5 (P = 0.006). There was no difference in headache, nausea, or vomiting. The number of hypertensive episodes increased from 0.045 to 0.086 during ramping (P = 0.125). Of 23 patients, only five (22%) had a marked decrease in symptoms; two of the three most symptomatic patients showed no significant improvement. Between dialysis sessions, patients complained of more fatigue and thirst (P < 0.0001 and P = 0.0028, respectively), and interdialytic weight gain following ramping was 5.1% of body weight compared with 4.4% without ramping (P < 0.0001). Blood pressure also increased following ramping, from 143/79 mm Hg to 152/81 mm Hg (P = 0.001). Ramping can decrease the overall number of side effects, but increases interdialytic symptoms, weight gain, and hypertension. In most instances, it simply changes the time the side effects occur. Only 22% of patients have significant benefit. These patients can be identified only through trial and error, as no model of these patients can be created.

Spontaneous tendon ruptures in patients on chronic dialysis

Large tendon rupture is a rare catastrophic occurrence in dialysis patients. Pathogenesis of this has been variably thought to be due to malnutrition, insufficient dialysis, amyloidosis, chronic acidosis, or hyperparathyroidism. We investigated contributory causes and timing of this complication in 44 dialysis patients (42 hemodialysis and two peritoneal dialysis patients). Five cases were our own; the other 39 were reported in the literature during the last two decades. Data were compared with a hospital database of 916 patients. The patients who experienced tendon ruptures had been on dialysis longer (mean duration, 7.6 years v 4.0 years; P = 0.001), were younger (mean age, 39.7 years v 48.4 years; P = 0.0001), had much higher parathyroid hormone levels (1,802 pg/mL v 202 pg/mL; P = 0.0001), had a higher phosphate level (6.8 mg/dL v 5.9 mg/dL; P = 0.001), had a slightly higher calcium level (9.2 mg/dL v 8.8 mg/dL; P = 0.038), and had a higher alkaline phosphatase level (649 IU/L v 109 IU/L; P = 0.0001) than control patients. Patients with tendon ruptures had no evidence of malnutrition (albumin 3.7 g/dL v 3.8 g/dL; P = 0.237) and had the same acidosis (bicarbonate 22.2 mEq/L v 22.0 mEq/L; P = 0.180). The time on dialysis to rupture was inversely related to the patients age (r = 0.47, P = 0.004). Most patients had evidence of years of poorly controlled hyperparathyroidism with high and increasing levels of parathyroid hormone and alkaline phosphatase. Previous steroid use was also much more common in patients with tendon ruptures, as was radiographic evidence of osteitis fibrosa. The disease led to long hospitalization and prolonged morbidity, with mobility limitations in several patients. Spontaneous large tendon rupture in patients is secondary to hyperparathyroidism; is more common in young patients, particularly if exposed to corticosteroids; leads to long-lasting morbidity; and should be preventable by better supervision and treatment of hyperparathyroidism.

PREGNANCY IN CHRONIC DIALYSIS : A REVIEW AND ANALYSIS OF THE LITERATURE

Pregnancy is uncommon in end-stage renal failure, particularly in patients requiring dialysis. We reviewed the literature from 1965 to date, seeking an optimal way of dialyzing pregnant women after encountering one such patient. Methods We searched the English literature by cross-referencing “pregnancy” with “hemo-” or “peritoneal dialysis” and “renal failure”. Eighty-six pregnancies worldwide were found to which we added one case of our own. Various independent factors were studied against gestational age at delivery using uni- and multivariate analysis. These factors included mothers age, previous delivery, diagnoses of renal disease, dialysis duration prior to pregnancy, gestational age at onset of dialysis, dialysis type, level of hemoglobin during pregnancy, BUN and creatinine targets, BUN/creatinine ratio, dialysis intensity at the beginning and end of pregnancy, influence of erythropoietin and dialysis complications. Results Of the 87 pregnancies, 12% resulted in stillbirths, 9% of neonates died prior to discharge. The mean gestational age at delivery was 32 ± 5 weeks, and the mean birth weight 1604 ± 652 g. Two congenital abnormalities and one twin pregnancy were reported. 48% of deliveries were premature. Pre-eclampsia was reported in 11%, and worsening hypertension in 17%. CAPD was used in 25 and hemodialysis in 62 patients. Fetal survival was similar in both cases (72% vs 82%), although incidence of various dialysis complications differed. The conventional dialysis goals of a low target BUN level and hemoglobin for pregnant patients were not factors in predicting fetal outcome. The number of hemodialyses/week were negatively correlated (R = -0.35, P = 0.061), but the hours of dialysis positively correlated (R = 0.42, p = 0.035) to gestational age. Fetal survival was independently influenced by creatinine level [564 µmol/L when baby survived vs 788 µmol/L when baby died (p = 0.021)], BUN/creatinine ratio (50 vs 30, p = 0.053), and hours of dialysis (5.6 hrs vs 3.6 hrs, p=0.013). There was no relation of either frequency or volume of peritoneal dialysis exchanges to gestational age or fetal survival. Conclusions Greater attention to a high intake of protein (>1.5 g/kg) and higher dose of hemodialysis, achieved by longer, every other day dialysis, may be the optimal approach to pregnant patients on hemodialysis. Our first attempt to define the goal of hemodialysis is to keep the predialysis creatinine below 600 mmol/L and the protein intake high enough so the predialysis BUN level is >25 mmol/L. There are no clear guidelines on how to best perform CAPD.

Emergency Treatment of Lithium-Induced Diabetes Insipidus with Nonsteroidal Anti-Inflammatory Drugs

Thiazides and amiloride are the most often suggested treatment for nephrogenic diabetic insipidus. We found this ineffectual in a patient with acute problems and reviewed the literature to see if there were other more efficient approaches. A 47-year-old woman on lithium had polyuria. When inadvertently fasted for 48 h she became confused, had a seizure, and her sodium was 170 mmol/L. Urinary output was 24 L/day. Large volumes of intravenous fluids were given but sodium remained > 170 mmol/L. Treatment with DDAVP, thiazides, and amiloride did not decrease urinary output. Indomethacin 150 mg was started and urine volume immediately fell to one-half. However, because of persistent high urine output the patient was then fluid depleted, with further reduction to normal in urine volume, and Na decreased to 140 mmol/L. Creatinine rose from 135 mumol/L to 173 mumol/L, but decreased to 152 mumol/L when indomethacin was decreased to 75 mg q.d.; urinary output remained stable around 2 L/day. The literature described 22 patients with nephrogenic diabetes insipidus (16 congenital, 6 lithium) treated with nonsteroidal anti-inflammatory drugs. Urine flow was reduced to 1/3, within hours. Rarely, mild renal failure ensued, improving in all but one case when nonsteroidal anti-inflammatory drugs were reduced. Indomethacin (and controlled volume reduction if continued high urine output), while observing renal function, appears the emergency treatment of choice for serious complications of nephrogenic diabetes insipidus.

Serious renal disease in Egypt.

We studied serious renal disease in Egypt by registering all 155 patients coming to the nephrology service at the University of Cairo during a period of 62 days in 1993. The patients presented with severe uremic symptoms. Admission creatinine and urea levels were high, 804 μmol/l and 64 mmol/l. Fifteen percent of the patients died; 115 underwent dialysis. Sixty patients presented with chronic renal failure; 53 with acute renal failure, but 24 of these were later found to have end-stage renal failure. Of 29 patients with true acute renal failure, 11 (38%) had pre-renal failure and 7 (24%) postrenal failure. Twenty-one patients were followed up after transplantation and chronic dialysis, another 17 had nephrotic syndrome, 3 hypertension, and one had asymptomatic urinary abnormalities. The most common specific etiology for chronic end-stage renal failure was diabetes mellitus type II in the older patients; second most common was Schistosoma in the younger ones. Most diabetic patients came from the city. All but one Schistosoma patient came from rural Egypt. In the 22 patients who underwent renal biopsy the most common diagnosis was mesangio capillary glomerulonephritis. The prevalence of acute renal failure, particularly iatrogenic-toxic, is increasing

The Anemia of Acute Renal Failure: Association with Oliguria and Elevated Blood Urea

Anemia is very frequent in patients with acute failure but the nature of the relationship between the two conditions has remained unclear. We studied all patients with well-documented acute renal failure seen in consultation by our nephrology division during 1991. Fifty-three of the 56 patients had at least mild anemia (hematocrit < 35%) at some point during their hospital stay. Forty-three of the patients had a hematocrit below 30% and 14 had a hematocrit below this level on admission. Twenty-four of the patients underwent major operations and all of these patients required blood transfusions. In this group there was a significant correlation between maximum serum urea and lowest hemoglobin (r = 0.4, p < .05) but no similar correlation between maximum creatinine and lowest hemoglobin. Oliguric patients had a mean lowest hemoglobin of 7.3 +/- 0.4 g/dL, which was significantly lower than the value for nonoliguric patients, 9.0 +/- 0.4 g/dL. This study confirms the presence of anemia in 91% of patients with acute renal failure and shows it to be related to rise in urea and presence of oliguria. Clearly, however, the anemia is multifactorial, since in one-quarter of the patients it precedes onset of renal failure.

Individual differences in biocompatibility responses to hemodialysis

There are very few reports in the literature on individual differences in the response to dialysis treatment. We studied the influence of the individual patient, dialysis membrane quality, blood-flow (Qb) and surface area on leukocyte activation and complement generation (C3a) during 234 hemodialysis treatments using Cuprophan (CU), hemophane (HE) and polyamide (PA) dialyzers. The most common reaction was a decrease in leukocyte count and an increase in C3a after 15 minutes of treatment. Leukocyte overshoot by the end of dialysis was observed at high Qb for all three membranes but at low Qb only during CU treatments. The reaction patterns were influenced by the quality of the membrane, area and Qb. Analysis of each individual patient showed for a large number of treatments reaction patterns corresponding to those described in the literature. However, some patients reacted differently. In four patients (20%), the nadir in leukocyte count and maximum in C3a concentration was reached considerably later during CU-dialysis. Three patients were devoid of pronounced early leukocyte response but presented with the late overshoot during CU-dialysis. Three other patients reacted with an early drop in leukocyte count and a rapid increase in C3a generation during PA treatments but not during HE treatments. Three other patients reacted vice versa. A particular mode of dialysis treatment may thus be biocompatible for some patients but not necessarily for all. In the case biocompatibility is desired the individual response to the particular dialysis mode needs to be identified. The underlying mechanisms warrant further studies.

Differences in Dialysis Practice Are the Main Reasons for the High Mortality Rate in the United States Compared to Japan

The cumulative survival of Japanese hemodialysis patients is more than 2.5 times better than that of dialysis patients in the United States (U.S.). The difference is particularly pronounced in older patients, being 4 times better in patients over the age of 50 years. The mortality in U.S. patients has increased from 10 to 25% over the last three decades, but has remained stable at around 10% in Japan.

Patient related factors leading to slow urea transfer in the body during dialysis.

We studied the trans compartmental speed of urea transfer by comparing concentration changes of blood urea nitrogen to mass changes of urea during 80 dialyses in six patients. The speed of urea transfer was studied as a dependent factor of 15 patient characteristics: age; gender; fluid overload; and pre and post values of and change in pulse and temperature, calcitonin gene related peptide, and mean arterial blood pressure. Concentration changes in blood urea nitrogen were measured as pre and post dialysis urea concentration, the total urea in the body was measured by pre dialysis urea and tritium total body water determinations, and the actual mass of urea removed by collecting all dialysate. As a mean, concentration of blood urea nitrogen fell 54% but the mass urea removed was only 40% for a mean ratio of 1.41. Nine factors were associated with the speed of urea transfer. Patients with fast transfer had more normal fluid balance, a normal pulse rate, body temperature, calcitonin gene related peptide values, and blood pressure both before and after dialysis. The patients with a slower transfer of urea had a lower blood pressure before and after dialysis and a more labile pulse rate and body temperature. Patients with unpredictable urea transfer were the most edematous and had the most labile blood pressure. It is important to know which patients have slow urea transfer. Such patients should not be treated by fast dialysis, and those with the slowest rates may do particularly well on continuous ambulatory peritoneal dialysis. A number of fairly simple clinical parameters such as fluid overload, body temperature, and pulse rate and blood pressure before and after dialysis, may identify such patients. If undetected, such patients will be underdialyzed, their protein intake established by protein catabolic rate will be overestimated, and they will have an increased morbidity and mortality.

All elderly patients should be offered dialysis

1. n nPhysicians practise age rationing in dialysis. n n n n n2. n nThere is no medical, quality of life, economical or moral argument for rationing out the old from dialysis. n n n n n3. n nRationing by age is unjust, unethical, and immoral. n n n n n4. n nGovernments will increase their pressure on physicians to limit treatment. n n n n n5. n nThere is no reasonable way to ration dialysis. n n n n n6. n nPhysicians are therefore likely to follow the path of least resistance, and let age be the rationing tool under various subterfuges. n n n n n7. n nSuch a scheme will wipe out medicine as a profession and make physicians into body technicians. n n n n n8. n nTo avoid this, the fifth principle, the duty of advocacy, needs to be established as an important professional duty of physicians. n n n n n9. n nTo avoid the dilemma of torturing dialysis patients who do badly, all dialysis must begin with a 30-day trial, at the end of which time dialysis will either be continued if the patient is doing well, or discontinued if not. n n n n n10. n nTo ease the problem of discontinuation of dialysis later, patients must let their wish be known of what to do if incompetent, thus advance directives.