Aggiornamento
Ematuria e proteinuria
Haematuria and proteinuria
Fabiola Scaramuzzino1, Francesca Burlo2, Giulia Delcaro2, Martina Peinkhofer2, Marco Sutera2, Sabrina Persia1, Francesco Emma3
1Scuola di Specializzazione in Pediatria, Università “Tor Vergata”, Roma
2Scuola di Specializzazione in Pediatria, Università di Trieste
3IRCCS Ospedale Pediatrico “Bambino Gesù”, Roma
Settembre 2024 - pagg. 425 -434 | DOI: 10.53126/MEB43425
Abstract
Proteinuria and haematuria are common findings in children. However, they are indicative of a renal or urinary condition only in a minority of cases. The probability of an underlying disease causing haematuria and /or proteinuria increases when they are associated and in the presence of symptoms that suggest kidney damage, such as oedema, hypertension, or kidney failure. Transient and orthostatic proteinurias are benign conditions that do not require further investigations. Proteinuria should always be investigated when constant or heavy. If patients present with nephrotic syndrome, oedema and hypoalbuminemia, proteinuria is always pathologic. Tubular proteinuria should always be ruled out, in particular in male subjects with persistent proteinuria. Haematuria can be glomerular or non-glomerular and may present as gross haematuria or can only be detected microscopically. Macroscopic haematuria should always be investigated as it may be associated with benign conditions (fever, exertion, dehydration, nutcracker syndrome), but also with several conditions such as glomerular diseases or urolithiasis. The urine colour, the urinary sediment, the morphology of red blood cells, kidney function, the presence of proteinuria and the medical history help in the differential diagnosis. On the other hand, microscopic haematuria should be investigated only when persistent or if there is a positive family history. This paper presents 5 illustrative cases to highlight the above points.
Riassunto
Proteinuria ed ematuria sono condizioni frequenti in età pediatrica che spesso vengono riscontrate in maniera occasionale. Tali riscontri sono indicativi di patologia renale solo in una minoranza di casi, che aumenta considerevolmente quando queste condizioni si presentano in maniera associata o quando emergono in presenza di segni o sintomi suggestivi di danno renale, quali edemi, ipertensione, o insufficienza renale. Quando la proteinuria viene riscontrata in maniera transitoria o quando è associata all'ortostatismo, questa è benigna e non va indagata ulteriormente. Diversamente, la proteinuria deve sempre essere attenzionata quando si presenta in maniera persistente o in quantità elevate. In presenza di sindrome nefrosica caratterizzata da edemi e/o ipoalbuminemia, la proteinuria è sempre patologica. Soprattutto nei soggetti maschi, è importante escludere una proteinuria tubulare dosando una proteina urinaria di basso peso molecolare. L’ematuria può avere un’origine glomerulare o post-glomerulare. Può essere macroematuria o essere riscontrata solo tramite analisi delle urine. La macroematuria deve sempre essere indagata. Può associarsi a condizioni benigne (febbre, sforzo, disidratazione, sindrome dello schiaccianoci), ma anche a varie patologie renali, in particolare glomerulopatie e calcolosi. Il colore delle urine, il sedimento, la morfologia delle emazie, la funzione renale, l’associazione con proteinuria e la storia clinica possono guidare il pediatra nell’orientamento diagnostico. La microematuria, invece, va indagata quando persiste su più campioni o in presenza di familiarità. Presentiamo in questo lavoro 5 casi esemplificativi per illustrare questi vari aspetti.
Classificazione MeSH
Contenuto riservato
Per leggere l'articolo completo è necessario effettuare il login.
Non sei ancora registrato? Registrati
Bibliografia
1. Dodge WF, West EF, Smith EH, Bunce H. Proteinuria and hematuria in schoolchildren: Epidemiology and early natural history. J Pediatr 1976;88(2):327-47. doi:10.1016/S0022-3476(76)81012-8.
2. Gattineni J. Highlights for the Management of a Child with Proteinuria and Hematuria. Int J Pediatr 2012;2012:1-7. doi: 10. 1155/2012/768142.
3. Pasini A, Benetti E, Conti G, et al. The Italian Society for Pediatric Nephrology (SINePe) consensus document on the management of nephrotic syndrome in children: Part i - Diagnosis and treatment of the first episode and the first relapse. Ital J Pediatr 2017;43 (1):1-15. doi: 10.1186/s13052-017-0356-x.
4. Trautmann A, Boyer O, Hodson E, et al.; International Pediatric Nephrology Association. IPNA clinical practice recommendations for the diagnosis and management of children with steroid-sensitive nephrotic syndrome. Pediatr Nephrol 2023;38(3):877-919. doi: 10.1007/s00467-022-05739-3.
5. Consensus della Società Italiana di Nefrologia Pediatrica (SINePe). La sindrome nefrosica in età pediatrica. Medico e Bambino 2019;38(9):577-88.
6. Conversano E, Galimberti AMC, Bevacqua M. Sindrome nefrosica: raccomandazioni terapeutiche oltre le linee guida SINePe. Medico e Bambino 2020;39(9):591-5. doi: 10.53126/ MEB39591.
7. Vivarelli M, Gibson K, Sinha A, Boyer O. Childhood nephrotic syndrome. Lancet 2023;402(10404):809-24. doi: 10.1016/S0140-6736(23)01051-6.
8. Jalanko H. Congenital nephrotic syndrome. Pediatr Nephrol 2009;24(11):2121-8. doi: 10.1007/s00467-007-0633-9.
9. Boyer O, Schaefer F, Haffner D, et al. Management of congenital nephrotic syndrome: consensus recommendations of the ERKNet-ESPN Working Group. Nat Rev Nephrol 2021;17(4):277-89. doi: 10.1038/s41581-020-00384-1.
10. Trautmann A, Vivarelli M, Samuel S, et al.; International Pediatric Nephrology Association. IPNA clinical practice recommendations for the diagnosis and management of children with steroid-resistant nephrotic syndrome. Pediatr Nephrol 2020;35(8):1529-61. doi: 10.1007/s00467-020-04519-1.
11. Nielsen R, Christensen EI, Birn H. Megalin and cubilin in proximal tubule protein reabsorption: From experimental models to human disease. Kidney Int 2016;89(1):58-67. doi: 10.1016/j.kint.2015.11.007.
12. Willnow TE. Nanotubes, the fast track to treatment of Dent disease? Kidney Int 2017; 91(4):776-8. doi: 10.1016/j.kint.2016.12.030.
13. Klootwijk ED, Reichold M, Unwin RJ, Kleta R, Warth R, Bockenhauer D. Renal Fanconi syndrome: taking a proximal look at the nephron. Nephrol Dial Transplant 2015;30 (9):1456-60. doi: 10.1093/ndt/gfu377.
14. Hall AM, Trepiccione F, Unwin RJ. Drug toxicity in the proximal tubule: new models, methods and mechanisms. Pediatr Nephrol 2022;37(5):973-82. doi: 10.1007/s00467-021-05121-9.
15. Joyce E, Glasner P, Ranganathan S, Swiatecka-Urban A. Tubulointerstitial nephritis: diagnosis, treatment, and monitoring. Pediatr Nephrol 2017;32(4):577-87. doi: 10.1007/ s00467-016-3394-5.
16. Jin YY, Huang LM, Quan XF, Mao JH. Dent disease: classification, heterogeneity and diagnosis. World J Pediatr 2021;17(1):52-57. doi: 10.1007/s12519-020-00357-1.
17. Ehlayel AM, Copelovitch L. Update on Dent Disease. Pediatr Clin North Am. 2019; 66(1):169-178. doi: 10.1016/j.pcl.2018.09.003.
18. Cebotaru V, Kaul S, Devuyst O, et al. High citrate diet delays progression of renal insufficiency in the ClC-5 knockout mouse model of Dent’s disease. Kidney Int 2005;68(2):642-52. doi: 10.1111/j.1523-1755.2005.00442.x.
19. Copelovitch L, Nash MA, Kaplan BS. Hypothesis: Dent disease is an underrecognized cause of focal glomerulosclerosis. Clin J Am Soc Nephrol 2007;2(5):914-8. doi: 10.2215/ CJN.00900207.
20. Leung AK, Wong AH, Barg SS. Proteinuria in Children: Evaluation and Differential Diagnosis. Am Fam Physician 2017;95(4): 248-54.
21. Shin JI, Park JM, Shin YH, Lee JS, Kim MJ, Jeong HJ. Nutcracker syndrome combined with IgA nephropathy in a child with recurrent hematuria. Pediatr Int 2006;48(3): 324-6. doi: 10.1111/j.1442-200X.2006.02212.x.
22. Mazzoni MB, Milani GP, Persico C, et al. Nutcracker phenomenon and idiopathic IgA nephropathy. NDT Plus 2011;4(6):453-4. doi: 10.1093/ndtplus/sfr108.
23. Ozono Y, Harada T, Namie S, Ichinose H, Shimamine R, Nishimawa Y, Hara K. The "nutcracker" phenomenon in combination with IgA nephropathy. J Int Med Res 1995;23 (2):126-31. doi: 10.1177/030006059502300207.
24. Lippi G, Sanchis-Gomar F. Exertional hematuria: definition, epidemiology, diagnostic and clinical considerations. Clin Chem Lab Med 2019;57(12):1818-28. doi: 10.1515/cclm-2019-0449.
25. Bowen DK, Tasian GE. Pediatric Stone Disease. Urol Clin North Am 2018;45(4):539-50. doi: 10.1016/j.ucl.2018.06.002.
26. Tasian GE, Copelovitch L. Evaluation and medical management of kidney stones in children. J Urol 2014;192(5):1329-36. doi: 10.1016/j.juro.2014.04.108.
27. Granata A, Distefano G, Sturiale A, et al. From Nutcracker Phenomenon to Nutcracker Syndrome: A Pictorial Review. Diagnostics (Basel) 2021;11(1):101. doi: 10.3390/diagnostics11010101.
28. Meyer J, Rother U, Stehr M, Meyer A. Nutcracker syndrome in children: Appearance, diagnostics, and treatment - A systematic review. J Pediatr Surg 2022;57(11):716-22. doi: 10.1016/j.jpedsurg.2021.12.019.
29. Yoon T, Kim SH, Kang E, Kim S. Nutcracker Phenomenon and Syndrome May Be More Prevalent Than Previously Thought. Korean J Radiol 2022;23(11):1112-4. doi: 10.3348/kjr.2022.0617.
30. Kurklinsky AK, Rooke TW. Nutcracker phenomenon and nutcracker syndrome. Mayo Clin Proc 2010;85(6):552-9. doi: 10.4065/mcp.2009.0586.
31. Ananthan K, Onida S, Davies AH. Nutcracker Syndrome: An Update on Current Diagnostic Criteria and Management Guidelines. Eur J Vasc Endovasc Surg 2017;53(6): 886-94. doi: 10.1016/j.ejvs.2017.02.015.
32. Paranhos RM, De Souza Figueiredo GA, et al. Immunoglobulin A nephropathy in paediatrics: An up-to-date. Nephrology (Carlton) 2022;27(4):307-17. doi: 10.1111/nep.13987. 33. Heerspink HJL, Radhakrishnan J, Alpers CE, et al.; PROTECT Investigators. Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial. Lancet 2023;401(10388):1584-94. doi: 10.1016/S0140-6736(23)00569-X.
34. Fellström BC, Barratt J, Cook H, et al.; NEFIGAN Trial Investigators. Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial. Lancet 2017;389(10084):2117-27. doi: 10.1016/S0140-6736(17)30550-0.
35. He P, Wang H, Huang C, He L. Hematuria was a high risk for renal progression and ESRD in immunoglobulin a nephropathy: a systematic review and meta-analysis. Ren Fail 2021;43(1):488-99. doi: 10.1080/ 0886022X.2021.1879852.
36. Gutieŕrez E, Zamora I, Ballarín J, et al.; Grupo de Estudio de Enfermedades Glomerulares de la Sociedad Española de Nefrología (GLOSEN). Long-term outcomes of IgA nephropathy presenting with minimal or no proteinuria. J Am Soc Nephrol 2012;23(10): 1753-60. doi: 10.1681/ASN.2012010063.
37. Antonucci L, Fuiano L, Gargiulo A, et al. Childhood-onset IgA nephropathy: is long-term recovery possible? Pediatr Nephrol 2024;39(6): 1837-46. doi: 10.1007/s00467-023-06259-4.
38. Jarrick S, Lundberg S, Welander A, et al. Mortality in IgA Nephropathy: A Nationwide Population-Based Cohort Study. J Am Soc Nephrol 2019;30(5):866-76. doi: 10.1681/ ASN.2018101017.
39. Jais JP, Knebelmann B, Giatras I, et al. X-linked Alport syndrome: natural history in 195 families and genotype- phenotype correlations in males. J Am Soc Nephrol 2000; 11(4):649-57. doi: 10.1681/ASN.V114649.
40. Rheault MN. Women and Alport syndrome. Pediatr Nephrol 2012;27(1):41-6. doi: 10.1007/s00467-011-1836-7.
41. Kashtan CE. Alport Syndrome: Achieving Early Diagnosis and Treatment. Am J Kidney Dis 2021;77(2):272-9. doi: 10.1053/j.ajkd. 2020.03.026.
42.Kashtan CE, Gross O. Correction to: Clinical practice recommendations for the diagnosis and management of Alport syndrome in children, adolescents, and young adults-an update for 2020. Pediatr Nephrol 2021;36(3):731. doi: 10.1007/s00467-020-04892-x. Erratum for: Pediatr Nephrol 2021;36(3):711-9.
43. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int 2021;100(4S):S1-S276. doi: 10.1016/j.kint.2021.05.021.
44. Gross O, Licht C, Anders HJ, et al.; Study Group Members of the Gesellschaft für Pädiatrische Nephrologie. Early angiotensin-converting enzyme inhibition in Alport syndrome delays renal failure and improves life expectancy. Kidney Int 2012;81(5):494-501. doi: 10.1038/ki.2011.407.
45. Brown DD, Reidy KJ. Approach to the Child with Hematuria. Pediatr Clin North Am 2019;66(1):15-30. doi: 10.1016/j.pcl.2018.08. 003.
Corrispondenza: giulydelcaro@gmail.com