. 2018 Dec 17;11(Suppl 1):i14–i26. doi: 10.1093/ckj/sfy088

Table 1.

Summary of observational studies, suggesting possible prognostic indicators for childhood ADPKD (chronologically ordered)

Publication	Objective(s)	Study details	Result(s) and conclusion relevant in this context
Sedman et al. [66]	To define the natural history.	A prospective, long-term observational study of 154 children at-risk for ADPKD (family history), receiving a renal US on age (range) 22 weeks GA – 18 years, with a FU period of 7.6 ± 1.4 years^a in 68 children of which 19 were affected.	Two children progressed to ESKD <18 years (at age 3.5 and 15 years); both were diagnosed <1 year.
Sedman et al. [66]	To define the natural history.		Conclusion: Children diagnosed <1 year may have an early deterioration in renal function.
Fick et al. [64]	To define VEO ADPKD.	A prospective, long-term observational study of 11 children with VEO ADPKD (6 diagnosed in utero and 5 <1 year; from 8 families); with FU period of 6.8 years (3–15 years)^b.	Parental disease course did not predict the course in these children. In 3 of 8 families, a de novo mutation was demonstrated in the affected mother. Higher rate of female-to-female transmission as compared to null hypothesis of equal probability of gender distribution possibilities. Conclusion: Risk factors for VEO: transmission from mother to daughter, de novo mutation in affected parent.
Seeman et al. [69]	To perform 24 h ABPM.	A cross-sectional observational study of 32 children, aged 12.3 ± 4.7 years^a.	Conclusion: Blood pressure correlated with renal size, but not with GFR, concentrating capacity, PU and plasma renin activity.
Sharp et al. [13]	To evaluate PU and microalbuminuria.	A prospective, cross-sectional observational study of children at-risk for ADPKD (family history), of which 103 affected, aged 11.2 ± 0.4 years^a. They were classified as ‘non-ADPKD’ if no renal cysts on US, regardless of GLA result, as ADPKD if ≥1 renal cyst, and then subdivided in ‘moderate ADPKD’ (MADPKD) if 1-10 and ‘severe ADPKD’ (SADPKD) if >10 and VEO ADPKD in case of diagnosis <1 year.	Significantly higher protein excretion rate in ADPKD versus non-ADPKD and SADPKD versus MADPKD. Conclusion: PU may be a marker of more severe renal disease.
Fick-Brosnahan et al. [74]	To define risk factors for more rapid progression.	An observational study of 185 children aged 8.2 ± 0.4 years^a, with a FU period of 5.7 years^a in 108 patients.	No gender effect. Faster renal enlargement in children with early severe disease. Significantly larger kidneys at baseline in children with BP > p75. No conclusive data on PU and haematuria. Conclusion: Risk factors are renal enlargement early in life, having >10 renal cysts before age 12 years, and having BPs above the 75th percentile for age, height and gender.
Fick-Brosnahan et al. [74]	To define risk factors for more rapid progression.	Progression was assessed by the rate of increase in US renal volume; with 2 arbitrarily chosen definitions of ‘early severe disease’: renal volume > 25% above the mean for age in this study (in 28%) ≥10 cysts < 12 years (in 70%)
Seeman et al. [68]	To evaluate the relation between BP and renal size.	A cross-sectional observational study of 62 children, aged 12.3 ± 4.3 years^a.	Mean renal volume and number of cysts was significantly greater in hypertensive than in normotensive children. Renal volume correlated with daytime and night-time systolic and diastolic BP. Conclusion: Significant relationship between renal volume, renal length and number of renal cysts and BP.
Seeman et al. [73]	To evaluate the relation between renal concentrating capacity and BP.	A cross-sectional observational study of 53 children, aged 11.8 ± 4.4 years^a.	Significantly higher prevalence of AHT in children with decreased renal concentrating capacity (35%) than in children with normal renal concentrating capacity (5%).
Seeman et al. [73]			Conclusion: Decreased renal concentrating capacity should be considered as an early marker of functional impairment in ADPKD and a further risk factor for hypertension.
Shamshirsaz et al. [67]	To evaluate outcome in VEO ADPKD.	An observational study of 46 VEO children (5.5 ± 5.4 years^a) versus 153 non-VEO ADPKD children (10.4 ± 4.5 years^a), with a FU period of 4.1 year^a.	VEO children had more cysts and larger renal volumes than non-VEO children when adjusted for age; and were more likely to have high BP. Over 90% of VEO children maintained preserved eGFR well into childhood. In both groups, children diagnosed due to signs or symptoms had higher age-adjusted serum creatinine levels, lower age-adjusted creatinine clearances and GFRs, and a greater frequency of hypertension than children diagnosed due to screening. Conclusion: VEO and presence of symptoms at diagnosis are risk factors for disease progression.
Cadnapaphornchai et al. [9]	To evaluate LVMI, renal volume, renal function and microalbuminuria in relation to systolic and diastolic BP.	A cross-sectional observational study of 85 children and young adults, aged 12.8 ± 1 years^a.	Hypertensive and borderline hypertensive children had significantly higher LVMI than normotensive children, with no significant difference between hypertensive and borderline hypertensive groups. In all groups: significant correlation between renal volume and systolic and diastolic BP. Significantly larger renal volume in hypertensive children than in the borderline, with no significant difference between normotensive and borderline hypertensive groups. Conclusion: LVMI may be detected earlier than an increase in renal volume in children with ADPKD and borderline hypertension.
Fencl et al. [72]	To compare phenotypes between children with mutations in the PKD1/PKD2 genes.	A retrospective study on 50 PKD1 children aged 8.6 ± 5.4 years^a versus 10 PKD2 children aged 8.9 ± 5.6 years^a.	PKD1 children have more and larger renal cysts, larger kidneys and higher ambulatory BP than do PKD2 children. Renal cysts and enlarged kidneys detected prenatally are highly specific for children with PKD1. Conclusion: Similar PKD1/2 genotype–phenotype correlation as seen in adults.
Mekahli et al. [11]	To compare disease manifestations in children diagnosed by postnatal US screening versus those presenting with symptoms.	A retrospective study on 47 children aged 7.2 ± 4.4 years^a with a FU period of 5.7± 3.6 years^a.	66% diagnosed by screening versus 34% with symptoms. Similar proportions of nephromegaly, AHT, microalbuminuria and decreased eGFR in both groups. Conclusion: Clinically relevant manifestations occur, even in those without overt symptoms.
Helal et al. [70]	To evaluate GH as indicator of more rapid disease progression.	An observational study of 180 children, aged 10.9 years^a (4–18 years)^b, with a FU period of 5 years.	Patients with GH at baseline (18%) demonstrated an increased rate of total renal volume growth and a faster decline in creatinine clearance compared with those without GH at baseline (82%). Conclusion: GH may be used as an early marker for a more severe progression.
Cadnapaphornchai et al. [8]	To evaluate the utility of MRI for serial assessment of kidney and cyst volume.	A prospective, long-term observational study of 77 children and young adults, aged 13 ± 4 years^a, with a FU period of 5 years.	Hypertensive subjects demonstrated a greater increase in fractional cyst volume over time versus normotensive subjects. Cyst number increased more rapidly in hypertensive children. Conclusion: MRI is an acceptable means to follow kidney and cyst volume as well as cyst number.
Audrézet et al. [71]	To assess the frequency of additional variations in PKD1, PKD2, HNF1B, and PKHD1 associated with the familial PKD mutation.	A retrospective study on 42 children prenatally diagnosed with ADPKD at GA of 24 weeks^a and a FU period of 4.2 years^a.	Additional PKD variation(s); inherited from the unaffected parent when tested; were identified in 37% of patients compared to 14% in adult ADPKD (P=0.001). No HNF1B variations or PKHD1 biallelic mutations were identified. Conclusion: Disease severity is probably inversely correlated with the level of polycystin 1 function.
Nowak et al. [65]	To assess the association between VEO status and adverse clinical outcomes.	A longitudinal retrospective study on 70 VEO patients and 70 non-VEO patients diagnosed at 10 years (6–14 years)^c with a FU period until the age of 16 years (12–21 years)^c.	Significantly more ESRD events in VEO. VEO patients were more likely to develop AHT. Conclusion: VEO ADPKD represents a particularly high-risk group.
Massella et al. [10]	To evaluate ABPM, kidney function, BP treatment, and kidney US.	A retrospective cross-sectional study on 310 children aged 11.5 ± 4.1 years^a.	A significant association between a categorical cyst score and day- and night-time AHT and 24 h AHT was seen. Kidney length was significantly associated with night-time AHT. Conclusion: ABPM helps to identify children who are likely to progress faster.

Mean; or mean ± SD.

Median (range); median; or (range).

Median (interquartile range).

AHT, arterial hypertension; BP, blood pressure; FU, follow-up; GA, gestational age; GH, glomerular hyperfiltration; GLA, gene linkage analysis; PU, proteinuria; US, ultrasound.