الفهرس 
Cystatin cOnly 14 pages are availabe for public view
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Abstract
The increasing number of cancer survivors necessitates monitoring for the long term consequences of antineoplastic treatment
Kidneys are particularly exposed to potential toxic injury, they comprise less than 1% of the total body weight and receive 20-25% of cardiac output.
There is a paucity of data concerning late nephrotoxicity that may interfere with the child development and causes permanent morbidity
NHL survivors are at particular increased risk than ALL survivors of renal dysfunction and they deserve special attention on their follow up for early detection of renal dysfunction.
The search for kidney function biomarkers has continued for many years over the last decade, low- molecular weight proteins (LMWPs) such as cystatin c and neutrophil gelatinase-associated lipocalin (NGAL) have drawn the most attention.
The goals of the current work were to evaluate Renal function in former hematological cancer survivors after completion of their antineoplastic treatment and to determine the role of cystatin c and NGAL as a noval methods for detection of renal dysfunction in these children.
Our Case-group included 50 children (25 patients who suffered from acute lymphoblastic leukemia and treated with CCG protocol And 25patients who suffered from Non- hodgkin lymphoma and treated with LMB 1996 protocol )While 20 apparently healthy children of comparable age and gender represented the control group. The study has been performed at pediatric oncology departments at Zagazig university children Hospital and oncology department at Benha Specialized children hospital during the period from March 2014 to March 2015.
Full history taking including age of diagnosis of malignancy, protocols of chemotherapy used, other nephrotoxic medication ,previous history of renal disease or urinary tract infection, Careful clinical examination including weight, height, body mass index, Blood pressure and laboratory investigations that included routine follow up investigation (CBC, serum ferritin, complete urine analysis including, Liver function test, serum electrolytes). Neutrophil gelatinase-associated lipocalin (NGAL) level and cystatin c level were detected.
Glomerular filtration rate using four formula Glomerular filtration rate (eGFR) was estimated using the classic Schwartz (eGFRSch), Schwartz redux (eGFRSchred), and Filler (eGFRFiller) formulas and with the new Schwartz equation for patients with chronic kidney disease (eGFRSchCKD).
The results of the study revealed statistically lower body weight and BMI among cancer survivors as compared with controls be explained by the negative impact either physical or psychological impact of the disease itself and or its associated medication and illness like mucositis on the nutritional status of the diseased children.
Statistically significant higher urea and creatinine values were detected among cancer survivors of both types when compared to healthy children the properties of cystatin c for estimating GFR seems to be better than those of S.creatinine as cystatin c production is not dependant on age, gender, BMI or nutritional status.
S.NGAL is known to be one of the most significantly expressed proteins in the kidney following nephrotoxic or ischemic insult. Therefore, S.NGAL is thought to be a biomarker of acute kidney injury.
Significant correlation between S.NGAL, S.cystatin c and eGFR equations results were found in several studies.
Statistically significant lower eGFR by all formulas were obvious among cancer survivors of both types of cancer as compared with healthy subjects.. Non-statistically significant lower GFR were detected when comparing NHL survivors with those ALL survived after treatment. These findings documented the long term negative impact of malignancy of both types on renal function, Treatment with cytotoxic medications with well documented long-term nephrotoxic effect as ifosfamide(or platinum derivates may play a role but non of our patients were exposed to such medications.
While the invasive methods used for direct measurement of GFR may be ideal for monitoring renal function, they are less practical and cumber some especially for young children. The noval markers (cystatin c and NGAL) may provide a more accurate assessment of renal dysfunction in this at risk population.
Our results showed that S.cystatin was the highest among NHL survivors followed by ALL survivors than healthy control. The properties of cystatin c for estimating GFR seems to be better than those of S.creatinine as cystatin c production is not dependant on age, gender, BMI or nutritional status, So cystatin c had an increased diagnostic accuracy for reduced GFR when compared to S.creatinine
No significant correlation could be found between S.Cystatin and age at diagnosis, duration of follow up and BMI. Lack of correlation between S.cystatin and BMI again confirm its independence on patients anthropometric measures.
In parallel with cystatin c, S.NGAL showed significantly higher mean among cancer survivors particularly those diagnosed with NHL value when compared to healthy controls. This noval biomarker for renal function have been reported to have a high sensitivity and specificity of acute renal injury as well as in chronic kidney disease and It is documented as sensitive biomarker indicative of renal damage in CKD patients and renal transplant recipients.
Significant correlation between S.NGAL, S.cystatin c and eGFR equations results were concluded in all studied groups. S.cystatin was shown to have better correlation with GFR and explained by the effect of associated protinuria on S.NGAL level.
Clinically significant albuminuria (≥B++) have been determined in the current work. Our high incidence may be related to several factors including ,different cohort of survivors ,ages at diagnosis ,duration of follow up ,treatment protocols ,and different methods and cut-off of pathological protinuria or inaccuracy of dipstick method used in our screening that may be associated with tube positive results as in concentrated sample or contamination with antiseptic solution or medication.
As albuminuria is an important predictor of subsequent renal function and also for death in general population, meticulous evaluation of albuminuria should be carried for every cancer survivor at follow up visit.
Proper time referral and implementation of renal protective measures may improve the child quality of life and avoid such co-morbidity.