RISK FACTORS FOR CARDIOVASCULAR COMPLICATIONS IN CHILDREN WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

THE AIM: to identify the frequency and risk factors of cardiovascular lesions in children with ADPKD. PATIENTS AND METHODS: 54 children (27M/27F) with ADPKD were examined. The median age was 12 (IQR: 8.0;15.0) years. Standard two-dimensional echocardiogram was performed. LV mass (LVM) was calculated, normalized to height2.7 and estimated by centile tables. Relative wall thickness (RWT) was calculated. Patterns of abnormal LV geometry were defined as follows: LV concentric remodelling by normal LVMI and RWT ≥0.42; eccentric LV hypertrophy (LVH) by increased LVMI and RWT <0.42; concentric LVH by increased LVMI and RWT ≥0.42. We checked blood pressure with ABPM. Patients were divided into 3 groups according to three levels of BP: hypertension (HBP; greater than the 95th percentile for sex, age, and height), high normal blood pressure (HNBP; 90–95th percentile), and normotension (NBP; less than the 90th percentile). Total kidney volume (cm3) was assessed by ultrasound, corrected for standard body surface and estimated by centile tables. Renal scintigraphy with 99mTc-dimercaptosuccinic acid (DMSA) with the calculation of the integral index of capture (IIC) was performed. RESULTS: Hypertension was found in 42,5 % of cases, HNBP was in 18,5% of cases. HBP were detected more frequently in children with increased renal volume (cm3/1,73m2) more than 97‰+≥50% compared with children with renal volume less than 97‰: (p=0.03), RR=2.9 (95% CI:1.4-4.9). Changes in the structure and geometry of the LV were identified in 14.8% of cases (concentric LVH – 7,4%; eccentric LVH -3,7%; LV concentric remodeling -3,7%). Children with LVMI >90 percentile were more frequently detected systolic hypertension in the daytime, diastolic hypertension at night compared with children with LVMI <90 percentile: 54% vs. 18% (p=0.04), RR=1.81 (95% CI:0.93-3.5) and 55% vs. 16% (p=0.008), RR=2.2 (95% CI:0.98-4.6). LVMI in children with systolic and diastolic hypertension was significantly higher than in children with isolated diastolic hypertension: 34.15 (30.7; 39) vs. 22.77 (22.04; 23.5) (p = 0.03). Increased renal volume (cm3/1,73m2) more than 97‰ and decreased IIC by DMSA were detected more frequently in children with LVMI>90 percentile compared with children with LVMI <90 percentile: (p=0.04), RR=1.7 (95% CI:1.1-2.6) and (р=0.04), RR=1.8 (95% CI:1.1-3.07). CONCLUSION: Risk factor for hypertension in children with ADPKD is increased renal volume. Risk factors for the development of left ventricular hypertrophy are systolic hypertension in the daytime, diastolic hypertension at night, increased kidney volume, and decreased IIC by DMSA. 

1. Steinman TI. Polycystic kidney disease: a 2011 update. Curr Opin Nephrol Hypertens 2012; 21: 189–194

2. Grantham J, Cowley B, Torres VE. Progression of autosomal dominant polycystic kidney disease (ADPKD) to renal failure. The Kidney: Physiology and Pathophysiology 2000; 2: 2513–2536

3. Hateboer N, Dijk MA, Bogdanova N et al. Comparison of phenotypes of polycystic kidney disease types 1 and 2. European PKD1–PKD2 Study Group. Lancet 1999; 353: 103–107

4. Rahman E, Niaz FA, Al-Suwaida A et al. Analysis of causes of mortality in patients with autosomal dominant polycystic kidney disease: a single center study. Saudi J Kidney Dis Transpl 2009; 20(5): 806-810

5. Ecder T, Schrier RW. Hypertension in autosomal-dominant polycystic kidney disease: early occurrence and unique aspects. J Am Soc Nephrol 2001; 12(1): 194-200

6. Schrier RW, Johnson AM, McFann K et al. The role of parental hypertension in the frequency and age of diagnosis of hypertension in offspring with autosomal-dominant polycystic kidney disease. Kidney Int 2003; 64: 1792-1799

7. Seeman T, Dusek J, Vondrichova H, et al. Ambulatory blood pressure correlates with renal volume and number of renal cysts in children with autosomal dominant polycystic kidney disease. Blood Press Monit 2003; 8: 107–110

8. Sans AL, Roca-Cusachs A, Torra R et al. Relationship between renal size and blood pressure profile in patients with autosomal dominant polycystic kidney disease without renal failure. Nefrologia 2010; 30: 567–572

9. Chapman AB, Johnson AM, Rainguet S et al. Left ventricular hypertrophy in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 1997; 8: 1292–1297

10. Valero FA, Martinez-Vea A, Bardaji A et al. Ambulatory blood pressure and left ventricular mass in normotensive patients with autosomal dominant polycystic kidney disease. J Am Soc Nephrol 1999; 10: 1020–1026

11. Zeier M, Geberth S, Mondelboum A et al. Elevated blood pressure profile and left ventricular mass in children and young adults with autosomal dominant polycystic kidney disease. J Am Soc Nephrol 1993; 3: 1451-1457

12. Cadnapaphornchai MA, McFann K, Strain JD et al. Increased left ventricular mass in children with autosomal dominant polycystic kidney disease and borderline hypertension. Kidney Int 2008; 74: 1192–1196

13. Ivy DD, Shaffer EM, Johnson AM et al. Cardiovascular abnormalities in children with autosomal dominant polycystic kidney disease. J Am Soc Nephrol 1995; 5: 2032–2036

14. Helal I, Reed B, Mettler P et al. Prevalence of Cardiovascular Events in Patients with Autosomal Dominant Polycystic Kidney Disease Am J Nephrol 2012; 36: 362–370 DOI: 10.1159/000343281

15. Gabow PA, Kimberling WJ, Strain JD et al. Utility of ultrasonography in the diagnosis of autosomal dominant polycystic kidney disease in children. J Am Soc Neph 1997; 8(1): 105–110

16. Reed B, McFann K. Presence of de novo mutations in autosomal dominant polycystic kidney disease patients without family history. Am J Kidney Dis 2008; 52(6): 1042

17. Pei Y, Obaji J, Dupuis A et al. Unified criteria for ultrasonographic diagnosis of ADPKD. J Am Soc Nephrol 2009; 20(1): 205–212

18. Schwartz GJ, Brion LP, Spizer A. The use of plasma creatinine concentration in for astimating glomerular filtration rate in infants, children and adolescents. Pediatr Clin North Am 1987; 34: 571–590

19. National Kidney Foundation Kidney Disease Outcomes Quality Initiatives K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease Evaluation Classification Stratification. Am J Kidney Dis 2002; 39: 1–266

20. Bakker J, Olree M, Kaatee R, et al. Renal volume measurements: accuracy and repeatability of US compared with that of MR imaging. Radiology 1999; 211: 623–628

21. Scholbach Th, Weitzel D. Body-Surface-Area Related Renal Volume: A Common Normal Range from Birth to Adulthood. Scientifica. http://dx.doi.org/10.6064/2012/949164.

22. Soergel ML, Kirschtein M, Busch C. Oscillometric twenty four hour ambulatory blood pressure values in healty children and adolescents: a multicenter trial including 1141 subjects. J Pediatr 1997; 130: 178-184

23. De la Sierra A, Segura J, Gorostidi M et al. Diurnal blood pressure variation, risk categories and antihypertensive treatment. Hypertens Res 2010; 33: 767–771

24. De Simone G, Danielis SR, Devereux RB et al. Left ventricular mass and body size in normotrnsive children and adults: Assessment of allometric relations and impact of overweight. J Am Coll Cardiol 1992; 20: 1251-1260.

25. Khoury PR, Mitsnefes M, Daniels SR et al. Age-specific reference intervals for indexed left ventricular mass in children. J Am Soc Echocardiogr 2009; 22: 709-714

26. Ganau A, Devereux RB, Roman M et al. Patterns of left ventricular hypertrophy and geometric remodeling in essential hypertension. J Am Coll Cardiol 1992; 19 (7): 1550-1558

27. Flynn JТ. Evaluation and management of hypertension in childhood. Prog Pediatr Cardiol 2001; 12: 177-188

28. Mitsnefes M, Flynn D, Cohn S et al. Masked Hypertension associates with left ventricular hypertrophy in children with CKD. J Am Sos Nephrol 2010; 21(1): 137-144

29. Shroff R, Weaver DJ, Mitsnefes M et al. Cardiovascular complications in children with chronic kidney disease. Nat Rev Nephrol 2011; 7: 642–649

30. Massella L, Mekahli D, Paripovic D et al. High prevalence of hypertension in a European cohort of children with ADPKD: results of the ADPKiDs study. Pediatr Nephrol 2016;

31. : 1728 31. Torres VE, Donovan KA, Sicli G et al. Synthesis of renin by tubulocystic epithelium in autosomal dominant polycystic kidney disease. Kidney Int 1992; 42: 364–373

32. Loghman-Adham M, Soto CE, Inagami T, Cassis L. The intrarenal renin-angiotensin system in autosomal dominant polycystic kidney disease. Am J Physiol Ren Physiol 2004; 287(4): 775–788

33. Chapman AB, Schrier RW. Pathogenesis of hypertension in autosomal dominant polycystic kidney disease. Semin Nephrol 1991; 11: 653–660

34. Fick GM, Duley IT, Johnson AM et al. The spectrum of autosomal dominant polycystic kidney disease in children. J Am Soc Nephrol 1994; 4: 1654–1660

35. Chapman AB, Guay-Woodford LM, Grantham JJ et al. Renal structure in early autosomal-dominant polycystic kidney disease (ADPKD): The Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) cohort. Kidney Int 2003; 64: 1035–1045

36. Abernethy J, Borhani NO, Hawkins CM et al. Systolic blood pressure as an independent predictor of mortality in the Hypertension Detection and Follow-up Program. Am J Prev Me 1986; 3(2): 123-132

37. Mahmood SS, Levy D, Vasan R et al. The Framingham Heart Study and the Epidemiology of Cardiovascular Diseases: A Historical Perspective. Lancet 2014; 383 (9921): 999–1008

38. Kawamura J, Ito H, Sawanishi K, Yoshida OA. Simple Method of Predicting Progression of Polycystic Kidney Disease by 99mTc-Dimercaptosuccinic Acid Renal Scintigraphy. Urol Int 1980; 35:388–394 DOI:10.1159/000280355

39. Зоркин СН, Хворостов ИН, Борисов СА и др. Возможности ренопротективной терапии у больных с обструктивными уропатиями. Педиатрия 2007; 6: 24-28 [Zorkin SN, Hvorostov IN, Borisov SA i dr..Vozmozhnosti renoprotectivnoj terapii u bolnyh obstructivnymi uropatijami. Pediatrija 2007; 6: 24-28]

40. Фомин ДК, Яцык СП, Лепаева ТВ и др. Особенности развития нефросклероза у детей при обструктивных уропатиях по данным статической нефросцинтиграфии. Вестник РНЦРР 2008; http://vestnik.rncrr.ru/vestnik/v8/papers/fomin2_v8.htm

41. Braun WE. Autosomal dominant polycystic kidney disease: emerging concepts of pathogenesis and new treatments. Cleve Clin J Med. 2009; 76 (2): 97-104

42. Matteucci MC, Wuhl E, Picca S, Mastrostefano A et al. ESCAPE Trial Group. Left ventricular geometry in children with mild to moderate chronic renal insufficiency. J Am Soc Nephrol 2006; 17(1): 218-226

43. Clementi A, Virzi G.M, Brocca A et al. Cardiorenal Syndrome Type 4: Management Blood Purif 2013; 36 (3-4): 200-209. doi: 10.1159/000356369

44. Johnson AM, Gabow PA. Identification of patients with autosomal dominant polycystic kidney disease at highest risk for endstage renal disease. J Am Soc Nephrol 1997; 8(10):1560-1567 45. Cadnapaphornchai MA, McFann K, Strain JD, Masoumi A, Schrier RW: Prospective change in renal volume and function in children with ADPKD. Clin J Am Soc Nephrol 2009; 4: 820–829