Karlien Cransberg

Acute kidney injury is a frequent complication in critically ill neonates receiving extracorporeal membrane oxygenation: a 14-year cohort study

IntroductionNewborns in need of extracorporeal membrane oxygenation (ECMO) support are at high risk of developing acute kidney injury (AKI). AKI may occur as part of multiple organ failure and can be aggravated by exposure to components of the extracorporeal circuit. AKI necessitates adjustment of dosage of renally eliminated drugs and avoidance of nephrotoxic drugs. We aimed to define systematically the incidence and clinical course of AKI in critically ill neonates receiving ECMO support.MethodsThis study reviewed prospectively collected clinical data (including age, diagnosis, ECMO course, and serum creatinine (SCr)) of all ECMO-treated neonates within our institution spanning a 14-year period. AKI was defined by using the Risk, Injury, Failure, Loss of renal function, and End-stage renal disease (RIFLE) classification. SCr data were reviewed per ECMO day and compared with age-specific SCr reference values. Accordingly, patients were assigned to RIFLE categories (Risk, Injury, or Failure as 150%, 200%, or 300% of median SCr reference values). Data are presented as median and interquartile range (IQR) or number and percentage.ResultsOf 242 patients included, 179 (74%) survived. Median age at the start of ECMO was 39 hours (IQR, 26 to 63); median ECMO duration was 5.8 days (IQR, 3.9 to 9.4). In total, 153 (64%) patients had evidence of AKI, with 72 (30%) qualifying as Risk, 55 (23%) as Injury, and 26 (11%) as Failure. At the end of the study period, only 71 (46%) patients of all 153 AKI patients improved by at least one RIFLE category. With regression analysis, it was found that nitric oxide ventilation (P = 0.04) and younger age at the start of ECMO (P = 0.004) were significant predictors of AKI. Survival until intensive care unit discharge was significantly lower for patients in the Failure category (35%) as compared with the Non-AKI (78%), Risk (82%), and Injury category (76%), with all P < 0.001, whereas no significant differences were found between the three latter RIFLE categories.ConclusionsTwo thirds of neonates receiving ECMO had AKI, with a significantly increased mortality risk for patients in the Failure category. As AKI during childhood may predispose to chronic kidney disease in adulthood, long-term monitoring of kidney function after ECMO is warranted.

Kidney Transplantation Without Prior Dialysis in Children: The Eurotransplant Experience

Kidney transplantation without prior dialysis may prevent dialysis‐associated morbidity. We analyzed the outcome of 1113 first kidney transplants in children performed between 1990 and 2000 in the Eurotransplant community. Enlistment for a deceased donor kidney before start of dialysis (127/895, 14%) made dialysis redundant in 55% of cases. Mean residual creatinine clearance at transplantation of these patients was 8 mL/min/1.73 m2. Pre‐emptive transplantations of deceased donor kidneys showed less acute rejections (52% vs. 37% rejection‐free at 3 years, p = 0.039), compared to transplantations following dialysis. The difference in graft survival between non‐dialyzed and dialyzed patients (82% vs. 69% at 6 year) did not reach statistical significance (p = 0.055). No differences were noted after living donor transplantation. Multivariate analysis showed that the period of transplantation was the strongest predictor of graft survival (p < 0.001). Congenital structural abnormalities such as primary kidney disease predominated in nondialyzed patients as compared to dialyzed patients (p < 0.001); this factor did not influence graft survival. Based on our conclusion that pre‐emptive transplantation is at least as good as post‐dialysis transplantation, as well as on quality of life arguments, we recommend to consider pre‐emptive transplantation in children with end‐stage renal failure.

Long-term Follow-up of Renal Transplantation in Children: A Dutch Cohort Study

Background. Few data exist on long-term morbidity, overall survival, and graft survival of pediatric renal transplantation. Methods. The authors performed a long-term cohort study in all Dutch patients, born before 1979, with onset of end-stage renal disease (ESRD) between 1972 and 1992 at age 0 to 15 years. Data on graft survival and determinants of outcome were obtained by reviewing all medical charts. The health status was assessed by cross-sectional examination of surviving patients. Results. Three hundred ninety-seven transplantations were performed in 231 of all 249 patients, of whom 25 died with a functioning graft. Cardiovascular disease was the most prominent cause of death. Graft survival estimates for all transplantations were 59.2%, 45.3%, 35.4%, and 30.3% at 5, 10, 15, and 20 years, respectively. In comparison with azathioprine, cyclosporine as the immunosuppressant was associated with increased graft survival in retransplantations but not in first transplantations. Cross-sectional examination was performed on 110 patients. In 44 patients, the most recent graft survival exceeded 15 years. Co-morbidity was found in 40% of all patients; motor, hearing, or visual disabilities were found in 19%. Bone disease, headaches, itching, and tremors were the most reported disabling problems. Cyclosporine use was associated with hypertension and a history of epilepsy. Compared with all age-matched Dutch inhabitants, the educational attainment was low, and unemployment and parental dependency were high. Conclusions. The authors’ results emphasize the need for reducing cardiovascular disease and metabolic bone disease in pediatric ESRD, a policy toward less toxic antirejection therapy, a more strict treatment of hypertension, and more attention for schooling and social development toward independence.

Haemofiltration in newborns treated with extracorporeal membrane oxygenation: a case-comparison study

IntroductionExtracorporeal membrane oxygenation is a supportive cardiopulmonary bypass technique for patients with acute reversible cardiovascular or respiratory failure. Favourable effects of haemofiltration during cardiopulmonary bypass instigated the use of this technique in infants on extracorporeal membrane oxygenation. The current study aimed at comparing clinical outcomes of newborns on extracorporeal membrane oxygenation with and without continuous haemofiltration.MethodsDemographic data of newborns treated with haemofiltration during extracorporeal membrane oxygenation were compared with those of patients treated without haemofiltration in a retrospective 1:3 case-comparison study. Primary outcome parameters were time on extracorporeal membrane oxygenation, time until extubation after decannulation, mortality and potential cost reduction. Secondary outcome parameters were total and mean fluid balance, urine output in mL/kg/day, dose of vasopressors, blood products and fluid bolus infusions, serum creatinin, urea and albumin levels.ResultsFifteen patients with haemofiltration (HF group) were compared with 46 patients without haemofiltration (control group). Time on extracorporeal membrane oxygenation was significantly shorter in the HF group: 98 hours (interquartile range (IQR) = 48 to 187 hours) versus 126 hours (IQR = 24 to 403 hours) in the control group (P = 0.02). Time from decannulation until extubation was shorter as well: 2.5 days (IQR = 0 to 6.4 days) versus 4.8 days (IQR = 0 to 121.5 days; P = 0.04). The calculated cost reduction was €5000 per extracorporeal membrane oxygenation run. There were no significant differences in mortality. Patients in the HF group needed fewer blood transfusions: 0.9 mL/kg/day (IQR = 0.2 to 2.7 mL/kg/day) versus 1.8 mL/kg/day (IQR = 0.8 to 2.9 mL/kg/day) in the control group (P< 0.001). Consequently the number of blood units used was significantly lower in the HF group (P< 0.001). There was no significant difference in inotropic support or other fluid resuscitation.ConclusionsAdding continuous haemofiltration to the extracorporeal membrane oxygenation circuit in newborns improves outcome by significantly reducing time on extracorporeal membrane oxygenation and on mechanical ventilation, because of better fluid management and a possible reduction of capillary leakage syndrome. Fewer blood transfusions are needed. All in all, overall costs per extracorporeal membrane oxygenation run will be lower.

Long-term Health Status in Childhood Survivors of Meningococcal Septic Shock

OBJECTIVE To assess long-term health status in patients who survived meningococcal septic shock in childhood. DESIGN Medical and psychological follow-up of a cross-sectional cohort. SETTING Pediatric intensive care unit (PICU) of a tertiary care university hospital. PARTICIPANTS All consecutive patients with septic shock and purpura who required intensive care between 1988 and 2001. Intervention Patients and their parents were invited to our follow-up clinic 4 to 16 years after PICU discharge. OUTCOME MEASURES Health status was assessed with a standard medical interview, physical examination, renal function test, and the Health Utilities Index Mark 2 (HUI2) and 3 (HUI3). RESULTS One hundred twenty patients (response rate 71%) participated in the follow-up (median age at PICU admission, 3.1 years; median follow-up interval, 9.8 years; median age at follow-up, 14.5 years). Thirty-five percent of patients had 1 or more of the following neurological impairments: severe mental retardation with epilepsy (3%), hearing loss (2%), chronic headache (28%), and focal neurological signs (6%), like paresis of 1 arm. One of the 16 patients with septic shock-associated acute renal failure at PICU admission showed signs of mild chronic renal failure (glomerular filtration rate, 62 mL/min/1.73 m(2); proteinuria; and hypertension). Scores were significantly lower on nearly all HUI2 and HUI3 attributes compared with Dutch population data, indicating poorer health in these patients. CONCLUSIONS In patients who survived meningococcal septic shock in childhood, one-third showed long-term neurological impairments, ranging from mild to severe and irreversible. Patients reported poorer general health as measured by HUI2 and HUI3.

Estimation of the glomerular filtration rate in children: which algorithm should be used?

Glomerular filtration rate (GFR) in children can be estimated by the formula GFR=k×BH/Pcr (where BH is body height in centimetres and Pcr is the plasma creatinine concentration in micromoles per litre). For k, several values have been reported: k=38 (Counahan), k=40 (Morris) and k=48.7 (Schwartz). In this study the predictive performance of these formulae was compared with that of newly developed formulae. GFR measurements based on inulin concentration time curves were divided into an index (n=58) and a validation data set (n=48). In the index data set a value for k was derived by application of nonlinear mixed-effect modelling. This approach was also used to develop a formula that better explained the relationship between patient factors and GFR. Bias and precision of all formulae were calculated for the validation data set. In the index data set a value of 41.2 was found for k, which was close to the value k=40 (Morris). Both formulae estimated GFR well (bias <5%; precision 25%). Further modelling of the relationship between patient factors and GFR did not improve the predictive performance. In our hospital GFR was best estimated by the formula with k=40 and k=41.2. It is recommended that the optimal value for k be assessed locally.

Eculizumab as rescue therapy for atypical hemolytic uremic syndrome with normal platelet count

BackgroundAtypical hemolytic uremic syndrome (aHUS) in childhood is a rare disease with frequent progression to end-stage renal disease and a high recurrence after kidney transplantation. Eculizumab, a humanized monoclonal antibody that binds to complement protein C5, may be beneficial in the treatment of aHUS.Case-diagnosis/treatmentA 6-year-old girl developed aHUS with only slightly elevated C3d (4.4%), no mutations in complement factors, and no antibodies against factor H. Plasma exchange treatment was successful initially, until aHUS recurred. After reinitiating plasma exchange, normalization of the platelet count and improvement of hemolysis occurred, but renal function worsened. Renal function then improved dramatically promptly after the switch to eculizumab.ConclusionsThis case demonstrates that platelet count is not always a reliable marker for improvement of aHUS and that eculizumab can prevent dialysis in plasma-resistant aHUS patients.

Pediatric renal transplantations in the Netherlands

Abstract: In the Netherlands, pediatric kidney transplantation programs are available in four centers. We retrospectively analyzed the results obtained over the past decade. Between 1985 and 1995, 231 patients (139 boys) received 269 transplants, including 61 repeat. The recipients were aged 1.9–21.8 yrs (mean 10.9), the donors 0.3–63.3 yrs (median 11.4, mean 19.7). Immunosuppression consisted of corticosteroids, cyclosporin A and azathioprine, in various combinations and dosages. The patient survival during follow‐up was 97%. The overall graft survival was 73% at 1 yr and 60% at 5 yrs after transplantation. Major causes of graft loss were acute rejection (21%), thrombosis (12%) and chronic rejection (28%). Acute rejection episodes were noted in 74% of all grafts. First acute rejection episodes had a moderate predictive value for graft loss (relative risk (RR), compared to rejection‐free grafts, 5.9). First rejection episodes occurring later than 3 months after transplantation were considerably more predictive (RR 18.3) than early ones. Grafts from living related donors (n = 35) yielded a superior 5‐yr graft survival (77%) and remained free of rejection more often than grafts from adult cadaveric donors(43% vs. 25%). The results of pre‐emptive transplants were excellent (n = 13, 5‐yr survival 100%). Repeat transplants had the same results as primary transplants. Recipients younger than 4 yrs showed a poor 5‐yr graft survival of 38% (n = 13). Single kidney grafts from donors younger than 4 yrs (n = 35) had a 5‐yr graft survival of 44%. In contrast, kidneys from these young donors did well if transplanted en bloc (n = 10, 5‐yr graft survival 89%). These overall results are in line with those of others. The results may be improved by expansion of immunosuppressive therapy in the first year and by thrombosis prophylaxis in high‐risk patient–donor combinations. Better results may be expected from more extensive use of living related donations, pre‐emptive transplantation and en bloc transplantation instead of single kidneys of young donors.

Etiology and epidemiology of end-stage renal disease in Dutch children 1987–2001

In this retrospective study 351 children (<16.0 years) with end-stage renal disease (ESRD) accepted for renal replacement therapy (RRT) in the four Dutch pediatric centers were analyzed for the period 1987–2001. The data were compared with a previous study performed in 1979–1986. Eighty patients were of non-Dutch origin. An annual ESRD incidence of 5.8 patients per million of the child population (p.m.c.p.) was calculated, without significant changes with time. The final prevalence in Dutch children under 15 years of ESRD was 38.7 p.m.c.p. The most frequent primary renal disease leading to ESRD was urethral valves, with a significant increase vs. the previous observation period (14% vs. 6%). The distribution of primary renal diseases was similar in patients of non-Dutch origin and in Dutch patients. Peritoneal dialysis was the most frequent dialysis procedure initially applied (62% vs. 26% in the earlier observation period). Thirteen percent of all first transplantations (n=278) were pre-emptive and 19% from living donors. Five-year graft survival after a living-donor and a cadaver graft was 80% and 73%, respectively. Overall patient survival after 10 years on RRT was 94%.

Long-term nephrotoxicity in adult survivors of childhood cancer

BACKGROUND AND OBJECTIVES Because little is known about long-term treatment-related nephrotoxicity, the aim was to determine risk factors for renal impairment long after childhood cancer treatment. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Data from 763 adult childhood cancer survivors (414 men) were obtained during regular visits at the late-effects clinic between 2003 and 2009. Median follow-up time was 18.3 years (range=5.0-58.2). Glomerular function was assessed by estimated GFR (using the Modification of Diet in Renal Disease formula), urinary albumin creatinine ratio, and tubular function by urinary β2-microglobulin creatinine ratio. The association with treatment factors was analyzed with covariance analysis for estimated GFR and logistic regression for urinary albumin and urinary β2-microglobulin creatinine ratios. RESULTS Survivors treated with nephrectomy and abdominal irradiation had significantly lower estimated GFR than survivors not treated with nephrectomy/abdominal irradiation (estimated mean=90 ml/min per 1.73 m(2) versus 106, P<0.001). Estimated GFR was significantly lower in survivors after treatment with high-dose ifosfamide (88 versus 98, P=0.02) and high-dose cisplatin (83 versus 101, P=0.004) compared with survivors not treated with these regimen. Nephrectomy combined with abdominal radiotherapy (odds ratio=3.14, 95% confidence interval=1.02; 9.69) and high-dose cisplatin (odds ratio=5.19, 95% confidence interval=1.21; 22.21) was associated with albuminuria. High-dose ifosfamide (odds ratio=6.19, 95% confidence interval=2.45; 15.67) was associated with increased urinary β2-microglobulin creatinine ratio. Hypertension was present in 23.4% of survivors and 31.4% of renal tumor survivors. CONCLUSIONS Treatment with unilateral nephrectomy, abdominal radiotherapy, cisplatin, and ifosfamide was associated with lower estimated GFR. Persisting tubular damage was related to ifosfamide treatment.