Barry L. Warshaw

Progression to end-stage renal disease in children with obstructive uropathy.

The course of 54 patients (35 boys and 19 girls) with end-stage renal disease resulting from obstructive uropathy was reviewed. The mean age at the initial sign of obstructive uropathy was 3.5 years. Twenty-two patients (41%) manifested evidence of obstructive uropathy during the first year of life. The mean age at the time of onset of ESRD (dialysis) was 12.2 years and was similar in boys and girls. The mean time interval between the first sign of obstructive uropathy and the initiation of dialysis was nine years. Fourteen patients operated upon at less than one year of age developed ESRD one to 20 years (mean ten years) following their initial surgery. Progression to ESRD occurred despite appropriate surgical management, including corrective as well as diversionary urologic procedures. However, because the patients were selectively referred for care of ESRD, no assessment of the incidence of ESRD caused by obstructive uropathy was possible. The data indicate that prolonged follow-up periods are necessary to assess the ultimate outcome of renal function in young patients with obstructive uropathy. Despite early intervention and intact renal function for many years during childhood, progression to ESRD may occur.

Recovery of renal function and survival after continuous renal replacement therapy during extracorporeal membrane oxygenation.

Objective: To assess the outcome of pediatric patients supported by concomitant extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT). Design, Setting, and Patients: Acute kidney injury is associated with mortality in ECMO patients. CRRT in patients on ECMO provides an efficient and potentially beneficial method of acute kidney injury management. Concern that concomitant CRRT use increases the risk of developing anuria and chronic renal failure limits its use in some centers. We hypothesized that development of chronic renal failure is rare with concurrent ECMO and CRRT. We evaluated the outcomes of 154 ECMO/CRRT patients cared for over 10 yrs at a referral pediatric medical center. Interventions: None. Measurements and Main Results: Among 68 (44%) ECMO/CRRT survivors, 45 were assigned a pediatric risk, injury, failure, loss and end-stage (referred to as “pRIFLE”) score at CRRT initiation. Seventeen (38%) patients met the criteria for Risk, 15 (33%) for Injury, and 10 (22%) for Failure. Two Failure patients later met End stage criteria. Of all survivors, 18 (26%) required ongoing renal replacement therapy (15 required continuous veno-venous hemofiltration, two required peritoneal dialysis, and one patient required intermittent hemodialysis) post ECMO discontinuation. Renal recovery occurred in 65 (96%) of 68 patients before discharge. One neonatal patient had sepsis-induced renal injury on transfer, but had normal creatinine 1 month later. Two pediatric patients with vasculitis and primary renal disease at presentation (both meeting Failure criteria) developed end-stage renal disease. One received peritoneal dialysis and subsequent renal transplant. The other has diminished function without need for renal replacement therapy. Conclusion: In the absence of primary renal disease, chronic renal failure did not occur after concurrent use of CRRT with ECMO. Concern for precipitating chronic renal failure by using CRRT during ECMO is not substantiated by this large single-center experience. Consistent with previous reports, mortality is higher in patients receiving concomitant CRRT and ECMO compared with those receiving ECMO alone. Mortality is similar to patients requiring CRRT who are not on ECMO. Additional studies are warranted to determine the optimal role of CRRT use in ECMO patients.

Focal glomerulosclerosis and renal transplantation

Eighteen patients with corticosteroid-resistant nephrotic syndrome developed end-stage renal disease and received one or more renal allografts. The lesion of focal segmental glomerulosclerosis and/or of focal glomerular obsolescence was demonstrable in the native kidneys of each patient. Following transplantation, nephrosis developed in three recipients. Two recipients developed nephrosis at two weeks and nine months posttransplant in association with rejection; the lesion of FGS was present in association with chronic rejection. Only one recipient developed recurrence of nephrosis and FGS unrelated to rejection. This was manifested by immediate onset of nephrosis in two successive allografts and histologic evidence of the lesion of FGS. The immediate recurrence in successive allografts suggests a circulating factor responsible for the renal lesion in this patient and indicates a separate etiology for a small number of patients with corticosteroid-resistant nephrosis and FGS.

Hemolytic Uremic Syndrome Associated With InvasiveStreptococcus pneumoniae Infection

* Abbreviations: HUS = : hemolytic uremic syndrome • ECH = : Egleston Childrens Hospital • HSCH = : Hughes Spalding Childrens Hospital • SRCH = : Scottish Rite Childrens Hospital • CDC = : Centers for Disease Control and Prevention • CT = : computed tomography • BUN = : blood urea nitrogen • PT = : prothrombin time • PTT = : partial thromboplastin time • CSF = : cerebrospinal fluid • DIC = : disseminated intravascular coagulopathy Hemolytic uremic syndrome (HUS), the most common cause of acute renal failure in childhood, is characterized by acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia. The majority of HUS cases occur after infectious diarrhea, and most of these cases are associated with Escherichia coli O157:H7 infection.1 2 However, atypical cases of HUS also occur in the absence of infectious diarrhea, although less commonly.3 Among 117 children <18 years of age identified with HUS in the state of Minnesota from 1979 through 1988, 16 patients had no preceding diarrheal illness, and 6 had a respiratory illness prodrome.4 Invasive infection with Streptococcus pneumoniae has rarely been associated with atypical HUS cases.5-14 However, there are no published data on the prevalence of invasive pneumococcal infections among patients with HUS or on the prevalence of HUS cases associated with invasive S pneumoniae infection. We report 7 cases of S pneumoniae -associated HUS managed at three Atlanta childrens hospitals over a period of 3 years. Recognition of these cases encouraged us to review our recent experience and determine the frequency of S pneumoniae as a cause of HUS at our institutions. An ongoing pneumococcal disease surveillance project in the metropolitan Atlanta area enabled us to determine the incidence of HUS associated with systemic pneumococcal infection. Medical records from the three childrens hospitals in the metropolitan Atlanta area (Egleston Childrens Hospital [ECH], Hughes Spalding Childrens Hospital [HSCH], and Scottish Rite Childrens Hospital [SRCH]) were searched for all patients with HUS from January 1994 to December 1996 using International Classification of Diseases, Ninth Revision coding for nonimmune hemolytic anemia (283.1) and HUS (283.11). Case databases of pediatric nephrologists serving these three hospitals were also reviewed to determine the existence of HUS cases not captured by this chart search. Medical records of all patients …

Renal Transplantation in Children with Obstructive Uropathy

The outcome of renal transplantation was examined in 52 pediatric patients (mean age 13 years) whose primary renal disease was obstructive uropathy. The bladder was used at transplantation in 45 allograft recipients, 39 of whom had had a previous lower urinary tract operation or bladder defunctionalization. An ileal loop was used in 7 recipients. The 52 patients received 73 renal allografts from 58 cadaver and 15 live-related donors. Presently, 40 patients (77 per cent) have functioning allografts, 4 have returned to dialysis and 8 (15 per cent) have died. The results indicate that the outcome of renal transplantation in patients with obstructive uropathy is similar to that of other transplant recipients. Damaged and defunctionalized bladders may be used successfully in most cases. If necessary an ileal conduit is an effective alternative. Post-transplant urologic complications occur with increased frequency but with appropriate management allograft salvage and patient survival are excellent.

Hypertension secondary to a renin-producing juxtaglomerular cell tumor

1. Strauss HW, Harrison K, Langan JK, Lebowitz E, and Pitt B: Thallium-201 for myocardial imaging: relation of thallium-201 to regional myocardial perfusion, Circulation 51:641, 1975. 2. Hamilton GW, Trobaugh GB, Ritchie JL, Williams DL, Weaver WD, and Gould KL: Myocardial imaging with intravenously injected Thallium-201 in patients with suspected coronary artery disease. Analysis of technique and correlation with electrocardiographic coronary anatomic and ventriculographic findings, Am J Cardiol 39:347, 1977. 3. Weich HF, Strauss HW, and Pitt B: The extraction of thallium-201 by the myocardium, Circulation 56:188, 1977. 4. Ferrer PL, Gottlieb S, Garcia OL, and Miale A: Noninvasive diagnosis of anomalous left coronary artery in the young with thallium-201 myocardial imaging, Pediatr Res 11:389, 1977 (abstr). 5. Wesselhoeft H, Fawcett JS, and Johnson AL: Anomalous origin of the left coronary artery from the pulmonary trunk. Its clinical spectrum, pathology and pathophysiology based on a review of 140 cases with seven further cases, Circulation 38:403, 1968. 6. Venugopal P, and Subramanian S: Anomalous origin of the left coronary artery from the pulmonary artery. Definitive surgical treatment by saphenous vein interposition in a 17 month old child, Ann Thorac Surg 19:451, 1975. 7. Neches WH, Mathews RA, Park SG, Lenox CG, Zuberbuhler JR, Siewers RD, and Bahnson HT: Anomalous origin of the left coronary artery from the pulmonary artery. A new method of surgical repair, Circulation 50:582, 1974. 8. El-Said GM, Ruzyllo W, Williams RL, Mullins CE, Hallman GL, Cooley DA, and McNamara DG: Early and late results of saphenous vein graft for anomalous origin of left coronary artery from pulmonary artery, Circulation 48:11 l, 1973. 9. Chiariello L, Meyer J, Reul GJ, Hallman GL, and Cooley DA: Surgical treatment for anomalous origin of left coronary artery from pulmonary artery and cardiovascular surgery, Ann Thorac Surg 19:443, 1975. 10. Strauss HW, Pitt B, Rouleau J, Bailey IK, and Wagner HN: Atlas of Cardiovascular nuclear Medicine, St. Louis, 1977, The CV Mosby Company, pp 128-129.

The Effect of Chronic Furosemide Administration on Urinary Calcium Excretion and Calcium Balance in Growing Rats

Summary: This study was designed to determine the calciuretic effect of furosemide and its impact upon calcium balance during chronic (25 days) furosemide administration to growing rats. Experiments were performed on 18 six-wk-old rats. Nine animals received furosemide, and 9 served as controls. The administration of furosemide in a dose of 40 mg resulted in a significant increase in calcium excretion in the treated group; urinary calcium excretion almost doubled that of the controls during the first 24-hr collection (3.74 ± 0.44 mg in the treated animals compared with 1.90 ± 0.15 mg in the controls; P < 0.05). The average daily urinary calcium excretion during each of four subsequent 6-day periods remained approximately three-fold higher in animals which received furosemide compared with controls (P < 0.001 for each 6-day period). The furosemide-induced increase in urinary calcium excretion did not diminish with time. Sodium excretion did not significantly increase either acutely or chronically in response to furosemide. Daily urinary volume increased approximately 40 to 60% in the furosemide-treated group compared with that of the controls (P < 0.001). The cumulative calcium balance in the control group exceeded by 7% that of the furosemide-treated animals (2696.3 ± 20.8 mg versus 2518.6 ± 20.1 mg (P ±.001).The findings indicate that distal nephron compensatory mechanisms effecting sodium conservation following furosemide do not result in similar conservation of calcium. Calcium balance may be deleteriously affected.Speculation: The long-term effects of furosemide on calcium homeostasis in man are not known. This study in rats suggests that furosemide may have deleterious effects on calcium homeostasis. Similar effects in humans, particularly growing children, may result in decreased calcium balance and bone demineralization.

Prevalence of clinical rejection after surveillance biopsies in pediatric renal transplants: Does early subclinical rejection predispose to subsequent rejection episodes?

Abstract:  We analyzed rates of both SCR and CR in children receiving SB at three months post‐transplant to determine if SCR predisposed patients to acute CR. Acute rejection was defined according to Banff criteria to include borderline classification or higher. All cases of SCR and CR were treated with anti‐rejection protocols. Between October 2004 and July 2008, 89 SB were performed at three months post‐transplant. Twenty‐six cases of SCR were detected (29%). Sixteen patients experienced 22 episodes of biopsy‐proven CR occurring after SB, including seven episodes following SCR and 15 after normal SB. The onset of CR varied from one to 27 months after SB and occurred at similar intervals for cases with SCR and normal SB. The percentage of patients remaining free of CR at 30 months post‐transplant was similar in patients with SCR and normal SB. Renal function and graft survival at 30 months also were no different between patients with SCR and those with normal SB. Early‐SCR, when treated with rejection protocols, is not a prognostic indicator for subsequent CR episodes.

1604 THE HORMONAL BASIS OF IDIOPATHIC HYPERCALCIURIA (IH)

We examined 6 children with IH and their families to determine the etiology of IH. Family members were divided into 2 categories: Group 1 consisted of the 6 index cases, 5 parents with calculi and 3 siblings with unexplained hematuria; Group 2 included the remaining 15 family members without calculi or hematuria. Mean age and fasting urinary Ca (UCa mg/dL GF) were the same in Groups 1 and 2, but Group 1 had a greater calciuric response to oral Ca, higher serum Ca (mg/dL) and fasting calcitriol (pg/ml), and lower fasting parathyroid activity (cAMP: nmol/dL GF).Urinary Na, Mg, and P, serum P and calcidiol, and the renal phosphate threshold were similar in both groups and did not correlate with UCa.Conclusions: IH may arise from a primary disorder of Vitamin D metabolism leading to increased calcitriol synthesis and intestinal Ca absorption. The data do not support a renal phosphate leak or high Na intake as the cause of IH.

1109 HYPOPHOSPHATEMIA (HP) IN PEDIATRIC RENAL ALLOGRAFT RECIPIENTS(RAR)

HP following successful renal transplantation has been attributed to either antacid therapy or persistent hyperparathyroidism. The data of 115 RAR were reviewed to assess the relationship between serum phosphate levels and circulating PTH. No patient routinely received antacid therapy. HP (serum P04 <2.3 mg% >16 years of age; <2.5 mg% 12-16 years; <3.0 mg% 6-12 years; <3.5 mg% <6 years) was common during the initial 2 months posttransplant (PT); 46 of 87 RAR (53%) had HP in the first PT month, and 43 of 87 (51%) in the 2nd month. Between the 2nd and 6th month 10 of 88 (11%) had HP. Transient HP was observed on one or more occasions in 45 of 93 (48%) 6 months to 7 years PT. No patient in this group had persistent HP. PTH levels for the early PT period (<6 months) were available on 53 occasions in 34 RAR (serum creatinine <2.0 mg%), and are as follows:The incidence of HP did not correlate with the PTH level, and occurred on 4 occasions with normal levels. This data suggests that factors other than PTH and antacids must be implicated in the pathogenesis of HP PT. Since HP >6 months PT was always transient, a direct role for HP in PT osteopenia and growth impairment seems unlikely.