Defining demographic, clinical and laboratory characteristics of cystic kidneydiseases in children and investigation of factors causing progression

AIM: The aim of this study was to investigate the demographic, clinical, laboratory data and complications of patients diagnosed cystic kidney disease and evaluate early markers of renal injury and factors affecting the progression in patients diagnosed with simple renal cyst (SRC) and multicystic dysplastic kidney (MCDK). We aimed to suggest a long term follow-up plan for the SRC and MCDK patients who do not currently have a generally accepted follow-up guideline. MATERIAL AND METHOD: The medical files of children diagnosed with cystic kidney between June 2008 and June 2018 were retrospectively reviewed in the Department of Pediatric Nephrology of our hospital. The patients with SRC and MCDK were invited to participate into the study prospectively. Blood and urine samples were analyzed and ambulatory blood pressure was monitored cross-sectionally. Patients were compared with a healthy control group of similar age and gender. RESULTS: There were 397 patients diagnosed with kidney cyst. The diagnosis were SRC in 171 (43%), MCDK in 102 (25%), autosomal dominant polycystic kidney disease (ADPKD) in 45 (11%), autosomal recessive polycystic kidney disease (ARPKD) in 38 (9%), syndromic cystic kidney disease in 19 (4%) patients and the other group of cystic diseases in 22 (5.5%). The mean age of the patients with SRC were 10.8 ± 3.6 years, serum creatinine values were 0.48 ± 0.27 mg/dl. Ten patients (5.2%) had complex kidney cyst. 14 SRC patients accepted to participate in the prospective study. 24h microalbuminuria levels were 13.4 ± 3.4 mg/day in the SRC group and 5.06 ± 3.1 mg/day in the control group (p=0.014). Two patients with cyst sizes larger than 4.5 cm were hypertensive. The mean age of the patients with MCDK were 8.27 ± 4.5 years, serum creatinine values were 0.48 ± 0.3 mg/dl. MCDK were located on the left side in 57 (55%) patients. Ten (%9.8) children had undergone nephrectomy. No kidney tumor was detected. Additional urinary system anomalies were present in 34 (33%) patients, most frequent anomaly was vesicoureteral reflux. Stage-3 or more advanced chronic kidney disease (CKD) was present in four patients. In all of them, there was small or hydronephrotic contralateral kidney on the ultrasonographic evaluation. The rate of involution was 31.9% in 10 years. Compensatory hypertrophy in the contralateral kidney was present in 75 (88%) patients during 6.1 ± 2.3 years. 17 patients with MCDK patients accepted to participate in the prospective study. Using ambulatory blood pressure monitoring (ABPM), hypertension (HT) was detected in 9 (52%) patients of whom three had undergone nephrectomy. Three patients had masked HT and 4 had severe ambulatory HT. Blood pressure (BP) load was 31.6 ± 30.8, systolic BP load was 19.2 ± 18.5, diastolic BP load was 12.5 ± 14.1, mean systolic blood pressure was 115 ± 14.9 mmHg in patients with MCDK which was higher than the control group (p=0.006, p=0.007, p=0.010, p=0.024). When all cystic kidney patients undergoing ABPM were evaluated, among 31 patients, 11 (35%) patients had ambulatory HT and 6 had severe ambulatory HT. Blood pressure load was higher than the control group. All patients with masked hypertension had MCDK. Five (45%) hypertensive patients had elevated plasma renin activity. The mean age of the patients with ADPKD were 11.06 ± 4.3 years, serum creatinine values were 0.73 ± 1.6 mg/dl. Family history was present in 41 (91%) patients. Among 18 patient that underwent genetic evaluation, PKD1 gene and PKD2 gene mutations were present in 10 and in one patient, respectively. CKD was present in two cases. The mean GFR values of the remaining cases were 159.5 ± 47.6 ml/min/1.73m2. In these patients, hyperfiltration was present in 23 (53%) patients, microalbuminuria in 8 (17%) patients, proteinuria in 6 (13%) patients, and HT in 3 ( 6%) patients. The mean age of the patients with ARPKD were 65.9±68.2 months, serum creatinine values were 1.03 (0.13-3.26) mg/dl. Nineteen (50%) patients had ARPKD-related liver disease. Major congenital anomalies were present in 15 (39%) cases, great majority having the Potter's syndrome. All of them had died in the neonatal period with respiratory failure except one patient who had died due to hypoplastic left ventricle syndrome. PKHD1 mutation was present in 9 patients. All the remaining patients that survived the neonatal period were still alive and two had CKD. The mean age of the syndromic cystic kidney group was 9.6 ± 5.2 years, serum creatinine values were 1.12 ± 0.76 mg/dl. Ten (53%) cases had Tuberous sclerosis and their serum creatinine measurements were normal. Five patients had Joubert syndrome, three having polycystic kidneys and the other 2 having nephronophthisis. Two of them died due to non-renal reasons and all survivors had CKD. All 4 patients with Bardet Biedl syndrome had obesity and mental retardation, two had retinitis pigmentosa, and 3 had CKD. DISCUSSION: Cystic kidney diseases in children have a wide clinical spectrum ranging from an uncomplicated cyst to end stage renal disease. SRC and MCDK have been thought to have a benign course. However, early signs of renal damage may also be present in patients with SRC and MCDK in the childhood. We found that while the creatinine levels were not different from the control group in patients with SRC, urinary albumin excretion was significantly higher, and HT was present in some patients. Therefore, we suggest that patients with SRC shall be closely monitored for renal damage markers such as microalbuminuria and HT like the other well-known cystic diseases. In MCDK patients, CKD was present only in the patients that had ultrasonographic abnormalities in the contralateral kidney. Therefore, we suggest that, in the detailed ultrasonographic evaluation, if patients have normal contralateral kidneys, further imaging studies may not be needed. In addition, we suggest that conservative management is appropriate as the risk of malignancy in the dysplastic kidney does not increase and nephrectomy, itself, does not treat or prevent HT. In our study, we found a high rate of ambulatory and masked HT in the MCDK group. We suggest that ABPM should be included in routine MCDK follow-up protocol considering the adverse effects of HT on both the single functional kidney and cardiovascular system. We observed that the risk of HT increased in both groups and a significant cause of HT was renin release. ADPKD does not usually cause kidney dysfunction in childhood, but early renal damage markers e.g. hyperfiltration, microalbuminuria and proteinuria could be present and should be followed-up accordingly. ARPKD, if it is associated with pulmonary hypoplasia, has a high mortality in the neonatal period. The other ARPKD patients have a more favorable prognosis. CONCLUSION: Our data was compatible with the literature regarding the well-known demographic and clinical characteristics in all cystic kidney diseases. Our identification of the presence of markers of early renal damage, i.e. increased urinary albumin excretion and HT, in SRC and MCDK patients could lead to relevant changes in the follow-up protocol of these patients. However, since there were limited number of patients, further studies that involve larger cohorts are needed. Keywords: Cystic Kidney Disease in Children, Renal Cyst, Simple Renal Cyst, Multicystic Dysplastic Kidney, Microalbuminuria, Ambulatory Blood Pressure Monitoring, Hypertension