Single-Center Experience of Pediatric Cystic Kidney Disease and Literature Review

Abstract

Introduction: Pediatric cystic kidney disease (CyKD) includes conditions characterized by renal cysts. Despite extensive research in this field, there are no reliable genetics or other biomarkers to estimate the phenotypic consequences. Therefore, CyKD in children heavily relies on clinical and diagnostic testing to predict the long-term outcomes.

Aim: A retrospective study aimed to provide a concise overview of this condition and analyze real-life data from a single-center pediatric CyKD cohort followed during a 12-year period.

Methods and materials: Medical records were reviewed for extensive clinical, laboratory, and radiological data, treatment approaches, and long-term outcomes.

Results: During the study period, 112 patients received a diagnosis of pediatric CyKD. Male patients were more involved than female (1:0.93). Fifty-six patients had a multicystic dysplastic kidney; twenty-one of them had an autosomal dominant disorder; fifteen had an isolated renal cyst; ten had been diagnosed with autosomal recessive polycystic kidney disease; three had the tuberous sclerosis complex; two patients each had Bardet-Biedl, Joubert syndrome, and nephronophthisis; and one had been diagnosed with the trisomy 13 condition. Genetic testing was performed in 17.9% of the patients, revealing disease-causing mutations in three-quarters (75.0%) of the tested patients. The most commonly presenting symptoms were abdominal distension (21.4%), abdominal pain (15.2%), and oligohydramnios (12.5%). Recurrent urinary tract infections (UTI) were documented in one-quarter of the patients, while 20.5% of them developed hypertension during the long-term follow-up. Antibiotic prophylaxis and antihypertensive treatment were the most employed therapeutic modalities. Seventeen patients progressed to chronic kidney disease (CKD), with thirteen of them eventually reaching end-stage renal disease (ESRD). The time from the initial detection of cysts on an ultrasound (US) to the onset of CKD across the entire cohort was 59.0 (7.0-31124.0) months, whereas the duration from the detection of cysts on an US to the onset of ESRD across the whole cohort was 127.0 (33.0-141.0) months. The median follow-up duration in the cohort was 3.0 (1.0-7.0) years. The patients who progressed to ESRD had clinical symptoms at the time of initial clinical presentation.

Conclusion: This study is the first large cohort of patients reported from Croatia. The most common CyKD was the multicystic dysplastic kidney disease. The most common clinical presentation was abdominal distention, abdominal pain, and oliguria. The most common long-term complications were recurrent UTIs, hypertension, CKD, and ESRD.

Keywords: ADPKD; ARPKD; Bardet–Biedl syndrome; Joubert syndrome; cystic kidney disease; multicystic dysplastic kidney; nephronophthisis complex; tuberous sclerosis complex.

Figure 1

Cystic kidney disease as part of the ciliopathies’ spectrum. The name of the syndrome is written in bold and those of its most important associated genes in Italic. Abbreviations: ADPKD, autosomal dominant polycystic kidney disease; ARPKD, autosomal recessive polycystic kidney disease; BBS, Bardet–Biedl syndrome; JS, Joubert syndrome; NPHC, nephronophthisis complex; T13, trisomy 13; and TSC, tuberous sclerosis complex. Adapted from Refs. [3,9,13,14].

Figure 2

The final diagnosis of included patients. Abbreviations: ADPKD (autosomal dominant polycystic kidney disease), ARPKD (autosomal recessive polycystic kidney disease), BBS (Bardet-Biedl syndrome), IRC (isolated renal cyst), JS (Joubert syndrome), MCDK (multicystic dysplastic kidney), NPHC (nephronophthisis complex), T13 (trisomy 13), TSC (tuberous sclerosis complex).

Figure 3

Detection of cysts by ultrasound in antenatal or perinatal (≤28 days) period, or later during childhood. Abbreviations: ADPKD (autosomal dominant polycystic kidney disease), ARPKD (autosomal recessive polycystic kidney disease), BBS (Bardet-Biedl syndrome), IRC (isolated renal cyst), JS (Joubert syndrome), MCDK (multicystic dysplastic kidney), NPHC (nephronophthisis complex), T13 (trisomy 13), TSC (tuberous sclerosis complex).

Figure 4

Number of patients with positive family history and genetic testing. Note that not all the patients had genetic testing. Abbreviations: (ADPKD) autosomal dominant polycystic kidney disease; (ARPKD) autosomal recessive polycystic kidney disease; (BBS) Bardet-Biedl syndrome; (IRC) isolated renal cyst; (JS) Joubert syndrome; (MCDK) multicystic dysplastic kidney; (NPHC) nephronophthisis complex; (T13) trisomy 13; (TSC) tuberous sclerosis complex.

Figure 5

Presenting signs (A) and symptoms (B) of cystic kidney disease. Abbreviations: ADPKD (autosomal dominant polycystic kidney disease), ARPKD (autosomal recessive polycystic kidney disease), BBS (Bardet-Biedl syndrome), IRC (isolated renal cyst), JS (Joubert syndrome), MCDK (multicystic dysplastic kidney), NPHC (nephronophthisis complex), T13 (trisomy 13), TSC (tuberous sclerosis complex), UTI (urinary tract infection), BUN (blood urea nitrogen), pCr (plasma creatinine).

Figure 6

Percentage of patients with increased echogenicity (A) and diminished corticomedullary differentiation (CMD) (B) according to the diagnoses. Abbreviations: ADPKD (autosomal dominant polycystic kidney disease), ARPKD (autosomal recessive polycystic kidney disease), BBS (Bardet-Biedl syndrome), IRC (isolated renal cyst), JS (Joubert syndrome), MCDK (multicystic dysplastic kidney), NPHC (nephronophthisis complex), T13 (trisomy 13), TSC (tuberous sclerosis complex), RK (right kidney), LK (left kidney).

Figure 7

Overview of patients with rUTI, performed VCUG/ceVUS, detected VUR and employed antibiotic prophylaxis. Abbreviations: ADPKD (autosomal dominant polycystic kidney disease), ARPKD (autosomal recessive polycystic kidney disease), BBS (Bardet-Biedl syndrome), IRC (isolated renal cyst), JS (Joubert syndrome), MCDK (multicystic dysplastic kidney), NPHC (nephronophthisis complex), T13 (trisomy 13), TSC (tuberous sclerosis complex), rUTI (recurrent urinary tract infection), VCUG (voiding cystourethrography), ceVUS (contrast enhanced voiding ultrasonography), VUR (vesicoureteral reflux).

Figure 8

Outcome of study patients during the follow up. Abbreviations: ADPKD (autosomal dominant polycystic kidney disease), ARPKD (autosomal recessive polycystic kidney disease), BBS (Bardet-Biedl syndrome), IRC (isolated renal cyst), JS (Joubert syndrome), MCDK (multicystic dysplastic kidney), NPHC (nephronophthisis complex), T13 (trisomy 13), TSC (tuberous sclerosis complex), CKD (chronic kidney disease), ESRD (end-stage renal disease).

Figure 9

Antyhipertensive medications according to diagnosis. Abbreviations: ADPKD (autosomal dominant polycystic kidney disease), ARPKD (autosomal recessive polycystic kidney disease), BBS (Bardet-Biedl syndrome), IRC (isolated renal cyst), JS (Joubert syndrome), MCDK (multicystic dysplastic kidney), NPHC (nephronophthisis complex), T13 (trisomy 13), TSC (tuberous sclerosis complex), ACEi (angiotensin-converting enzyme inhibitor), CCB (calcium channel blocker).

Figure 10

Extrarenal manifestations according to diagnosis. Abbreviations: ADPKD (autosomal dominant polycystic kidney disease), ARPKD (autosomal recessive polycystic kidney disease), BBS (Bardet-Biedl syndrome), IRC (isolated renal cyst), JS (Joubert syndrome), MCDK (multicystic dysplastic kidney), NPHC (nephronophthisis complex), T13 (trisomy 13), TSC (tuberous sclerosis complex).

Figure 11

Important steps in the long-term management of children with CyKD.