Bruce Z. Morgenstern

Growth of children following the initiation of dialysis: a comparison of three dialysis modalities

Maintenance dialysis usually serves as an interim treatment for children with end-stage renal disease (ESRD) until transplantation can take place. Some children, however, may require dialytic support for an extended period of time. Although dialysis improves some of the problems associated with growth failure in ESRD (acidosis, uremia, calcium, and phosphorus imbalance), many children continue to grow poorly. Therefore, three different dialysis modalities, continuous ambulatory peritoneal dialysis (CAPD), cycler/intermittent peritoneal dialysis (CPD), and hemodialysis (HD), were evaluated with regard to their effects on the growth of children initiating dialysis and remaining on that modality for 6–12 months. Growth was best for children undergoing CAPD when compared with the other two modalities with regard to the following growth parameters: incremental height standard deviation score for chronological age [−0.55±2.06 vs. −1.69±1.22 for CPD (P<0.05) and −1.80±1.13 for HD (P<0.05)]; incremental height standard deviation score for bone age [−1.68±1.71 vs. −2.45±1.43 for CPD (P=NS) and −2.03±1.28 for HD (P=NS)]; change in height standard deviation score during the dialysis period [0.00±0.67 vs. −0.15±.29 for CPD (P=NS) and −0.23±.23 for HD (P=NS)]. The reasons why growth appears to be best in children receiving CAPD may be related to its metabolic benefits: lower levels of uremia, as reflected by the blood urea nitrogen [50±12 vs. 69±16 mg/dl for CPD (P<0.5) and 89±17 for HD (P<0.05)], improved metabolic acidosis, as indicated by a higher serum bicarbonate concentration [24±2 mEq/l vs. 22±2 for CPD (P<0.05) and 21±2 for HD (P<0.05)]. In addition, children undergoing CAPD receive significant supplemental calories from the glucose absorbed during dialysis. CAPD, and possibly, other types of prolonged-dwell daily peritoneal dialysis appear to be most beneficial for growth, which may be of particular importance for the smaller child undergoing dialysis while awaiting transplantation.

Serum sodium abnormalities in children.

Even though multiple mechanisms operate to maintain the serum sodium concentration within a narrow range, serum sodium concentration is frequently abnormal in hospitalized children. This article defines terms clinically useful in categorizing such disorders and provides an overview of the physiology of sodium and water homeostasis. The recognition and treatment of disorders associated with an abnormal serum sodium are then considered.

Peritoneal Dialysis Kinetics in Children

Peritoneal dialysis (PD) achieved what many consider to be status as an accepted therapeutic modality for children by being described as “widely used” in the eighth edition of Nelson’s Textbook of Pediatrics in 1964 [1]. After 22 years as an accepted procedure and 37 years since Swan and Gordon’s original reports of PD in children with acute renal failure [2], PD remains a procedure that is employed almost solely based upon the clinician’s previous experiences. A sizable but largely anecdotal and poorly controlled body of literature now exists concerning the kinetics of PD in children. This chapter will review the current state of our knowledge of PD kinetics—the study of transperitoneal solute and fluid movement.

INCREASED PERITONEAL PROTEIN LOSS IN PEDIATRIC PERITONEAL DIALYSIS

Significant protein loss through the peritoneum of children on peritoneal dialysis(PD)has been well documented. To investigate this phenomenon,8 children(mean age 10yrs,range 1-19)were studied. A single 8-hour isotope-labelled exchange was performed and timed dialysate samples were obtained. Data were analyzed by the model of Pyle. The model determines the diffusive and convective characteristics of the peritoneum:the mass transfer area coefficient (MTAC)and the reflection coefficient(RC). The MTAC is an area permeability product(ml/min)and the RC is the fraction of solute reflected at the membrane during the convection associated with ultrafiltration. The mean(±SD)MTAC and RC for urea were 17.7±7.9 ml/min/1.73m2 and 0.14±0.08 respectively,for creatinine 11.6±7.0 and 0.28±0.01, for uric acid 7.7±3.9 and 0.44±0.16, for glucose 9.4±2.9 and 0.49±0.17, and for idealized total protein(T.P.)0.12±.15 and 0.95±0.03. When compared with adult means, excepting T.P., these were not statistically significant. The MTAC for T.P. was larger than in adults(p<0.03),and the RC for T.P.was smaller than in adults(p<0.01). This increased MTAC together with the lower RC signify that protein losses in children exceed those in adults. These data imply a greater large molecular weight solute removal in children on PD,resulting in effective clearance of uremic toxins. This may account for the low frequency of clinically manifest uremia-related morbidity,e.g.peripheral neuropathy,in children on PD,despite relatively elevated serum BUN and creatinine concentrations.

Development of Pneumatosis Cystoides Intestinalis Following Transperitoneal Renal Transplantation in a Child

A 9 1/2-year-old female developed pneumatosis cystoides intestinalis (PCI) which was detected radiographically 4 1/2 months after transperitoneal cadaveric renal transplantation, during a period characterized by recurrent episodes of acute rejection. Radiographic evaluation was prompted by the development of cramping abdominal pain, distention, and tenderness localized to the region of the allograft, which occurred during one such episode. Pneumatosis was localized primarily to an area of colon that lay in direct contact with the allograft. Evaluation of the available clinical and roentgenographic evidence suggested that pneumatosis may have resulted from the development of a sympathetic inflammatory reaction within the bowel wall adjacent to the acutely inflamed allograft. Subsequent stabilization of renal function was associated with resolution of the pneumatosis over the ensuing 8 months without surgical intervention or additional medical therapy.

AUTONOMIC NERVOUS SYSTEM DYSFUNCTTION(AD)IN CHILDREN WITH END STAGE RENAL DISFASE: OOMPARISON OF HEMD-(HD) AND PFRTIONEAL(PD)DIALYSIS

Symptomatic hypotension complicated 53-87% of all treatments in 7 of our pediatric HD patients (HDP) despite modest ultrafiltration (<6% of estimated dry weight). The possible relationship of AD to this problem was evaluated in 12 dialysis patients (DP) aged 8.1-19.8 yrs, 5 of whom were receiving peritoneal dialysis(PDP),and in 7 controls (C) aged 8.0-16.5 yrs, using the heart rate (HR) response to the Valsalva Maneuver (VM) (straining to 40 mm Hg × 10 sec)and degree of beat-to-beat variability in the resting heart rate (BVHR). Studies were performed using a standard electrocardiograph; the Valsalva Ratio(VR)was calculated as the maximal RR interval following÷minimal RR interval during VM. BVHR was determined as the coefficient of variation(CV)of 150 successive RR intervals recorded during recumbency. All DP had normal cardiac function by echocardiography, and none had orthostatic hypotension. The mean VR for C (2.06±.23) was significantly higher than that for HDP(1.54±.19,p<.001),PDP (1.68±.18,p<.02),and the group as a whole (1.60±.19,p<.001). In most DP the abnormally low VR was due to a failure to develop adequate reflex bradycardia following the release of straining. The mean CV for C (.103±.034) was significantly higher than that for HDP (.042±.015,p<.001) but not PDP (.072±.015,p<.10). Moreover, the mean CV for HDP was significantly lower than that for PDP (p<.01). Mean hemoglobin concentrations were not significantly different in HDP (7.1±1.5 g/dl)vs. PDP(7.6±.94 g/dl,p>.40), nor were the observed disturbances attributable to differences in resting HR, supine mean arterial pressure,months on dialysis, or age. The data indicate that AD occurs commonly among pediatric DP. The observed pattern of disturbances is consistent with defective cardiac parasympathetic innervation, with HDP more severely affected than PDP. AD also may be unmasked more readily in HDP, since the higher ultrafiltration rates associated with HD require more effective cardiovascular reflex compensation. AD should be considered as a possible cause of recurrent, symptomatic hypotension in pediatric DP.

Treatment of Severe Hypertension in Children with Renal Disease

Severe hypertension and hypertensive emergencies in children most often occur in association with secondary forms of high blood pressure and may develop in children with previously unrecognized disease or as a sudden change in children with known hypertension. The term hypertensive crisis or hypertensive emergency is used to denote a clinical situation in which the blood pressure has been elevated for some period of time and ought to be lowered over minutes, or hours depending on the patient’s clinical status. The clinical presentation of hypertensive emergencies varies. Life threatening hypertensive symptoms, such as acute heart failure, pulmonary edema or neurologic changes require immediate lowering of the blood pressure. (Table I)

Uric Acid Perturbations in the Hemolytic Uremic Syndrome

Although hyperuricemia has been found in a large number of disorders, (1) its occurrence in the hemolytic uremic syndrome (HUS) is not generally appreciated. (2,3) In 1969, while performing studies of the transperitoneal movement of solute (4) (including uric acid) in children undergoing their initial dialysis, we observed marked hyperuricemia disproportionate to the degree of renal failure in two infants with HUS. We have subsequently confirmed these observations in a series of 26 children with HUS and have performed studies in rabbits in an effort to identify the mechanism(s) leading to hyperuricemia. This report has four objectives: 1) to review our experience with and interpretation of uric acid metabolism in patients with HUS, 2) to present data which provide information on possible mechanisms for the hyperuricemia, 3) to consider uric acid metabolism in experimental models of hemolysis and acute and chronic renal failure, and 4) to review available literature on the subject of uric acid metabolism in renal failure.

PREDICTIVE FACTORS AFFECTING FIRST PEDIATRIC CADAVERIC TRANSPLANT SURVIVAL

Transplantation remains the optimal replacement therapy for children with end stage renal disease. Cadaveric allograft survival (surv)has improved over the past decade. We reviewed our experience with 61 first cadaveric transplants performed from 1972 through 1982. Twenty-three recipients(38%)were female and 38(62%) were male;the mean age was 11.2 yrs.(range 2-19). Forty-two (69%) were white,18(29%)black,and 1(2%)hispanic. Thirty-five(57%)had received at least 5 random donor blood transfusions(trans). Thirty (50%)were matched for a minimum of 2 HLA A and B antigens (Ag). Proportional hazards analysis(Coxs model)was used to examine 5 explanatory variables:sex,age,race, ≥5 trans,and number(no.)of Ag matches. Sex,age,and race did not affect graft surv. In this population,trans alone did not improve transplant surv(p>0.2).The no. of Ag matches was positively correlated with graft surv.(B=-0.3, p<0.02).The combination of trans and Ag matching provided excellent allograft surv(94% at 1 yr.67% 5 yrs).This prompted an examination of the data including a variable termed AgTrans, a first-order interaction of no. of Ag matches and trans status. AgTrans was the strongest factor associated with prolonged surv.(B=-0.47, p<0.001).Use of the model predicts that at the time at which graft surv.would be 50% with <5 trans and no Ag matches, it would increase to 68% with a 2 Ag match,and increase further to 85% with both a 2 Ag match and ≥5 trans.In summary,Ag matching acts as an initiator in pediatric cadaveric transplantation and ≥5 trans act as a promotor of graft function.

Therapeutic Approach to the Child with Acute Renal Failure

Acute renal failure (ARF) may be defined as a symptom complex that occurs when body fluid homeostasis is impaired by the rapid loss of kidney function. The diagnosis and pathophysiology of ARF are considered elsewhere in this volume. The past few decades have brought about major advances in the treatment of the biochemical derangements, hypertension, and fluid imbalance associated with acute renal failure. With widespread availability of dialysis, mortality has markedly decreased; those deaths that do occur are related more to the primary disorder and its complications than to renal failure. Therapy for acute renal failure depends upon the nature or the degree of renal impairment.