Various presentations – usually presents as episode frank haematuria in otherwise well individual.
Can be microscopic haematuria post URTI but within 2-3 days, not delayed as in PSAGN.
Diagnosis requires biopsy – looks like HSP. IgA is found in kidney, no abnormality in blood levels!
Up to 20% progressive renal disease so not quite benign.
Inflammation in the concentrating tissue of the kidney can produce a range of manifestations:
Protein in urine is not usually symptomatic in itself, the urine may seem more frothy. It would not be until the loss of a substantial amount of protein leads to hypoalbuminaemia and oedema (nephrotic syndrome) that it would be apparent.
Accompanying symptoms will tend to guide you to a diagnosis eg purpuric rash (HSP), photodermatitis and/or arhtritis (SLE), heavy proteinuria without haematuria (minimal change glomerulonephropathy).
Dipstick testing is sensitive for proteinuria and haematuria, but urine protein/albumin:creatinine ratio is more reliable. On microscopy, red and white cell casts are pathognomic. Presence of red cells useful to exclude other causes of apparent haematuria.
Complement – some characteristic patterns.
If isolated low C3, and fits with PSAGN, diagnosis is clear. But check it normalizes in 3/12, else biopsy.
Biopsy – for definitive diagnosis. Although some conditions have patchy changes so sampling error possible.
or HSP. Usually preschool but any age! Boys more than girls. Vasculitis, leucocytoclastic with IgA predominance. EULAR criteria 2010.
Features:
Leukocytoclastic vasculitis with glomerular mesangial IgA deposits. Biopsy of patients with IgA nephropathy identical, and indeed both groups have defective IgA1 glycosylation, which may explain why they may aggregate and precipitate IgA in small vessel walls as well as in the glomerular mesangium.
Complications and relapse associated with age esp over 6yr. 50% relapse, usually within 6 weeks but can be up to a year later; 50% of those will relapse more than once. Treat with NSAIDs (unless renal involvement!) for joint pain, analgesics for abdo pain. Small study from Turkey found that Ranitidine reduced symptoms.
Steroids (prednisolone 1-2 mg/kg/day for 1-2 weeks) are suggested (grade 2 recommendation) within 3 days of onset of severe abdominal pain (defined as pain requiring hospital admission) or acute GI bleeding – after exclusion of intussusception, of course.
Steroids are also suggested for orchitis, after excluding torsion.
Reviewing 101 children with abdo involvement those who did not receive steroids had an average of 5 days of abdominal pain, whereas all those treated recovered within 24 to 48 hours of starting steroids (letter, J Pediatr Gastroenterol Nutr. 31(3):323-4, 2000).
Abdominal pain is a predictor of renal involvement, so maybe that’s the best reason for giving steroids… (Kidney Int 1998; 53:1755-9).
20 to 90% risk of renal disease, but generally mild (mostly just mild proteinuria and/or haematuria)! Normal urinalysis at day 7 has 97% negative predictive value for chronic renal disease [PLoS One 2012;7:e29512].
About 56% of those children with renal disease develop signs and symptoms of renal disease a week or more after presentation, although generally in first month. Can be up to 6 months later. Incidence of renal failure in HSP nephritis is just 2 to 5%. Risk factors are severe abdominal pain (OR=2.1), age >8yrs (OR=2.7), and relapsed HSP (OR=3).[Arch Dis Child. 2010 Nov;95(11):877-82. doi: 10.1136/adc.2009.182394]
A normal urinalysisNB Children who appear to recover may have significant renal disease many years later. (Lancet. 339:280282, 1992).
If more than 50% crescents on biopsy, then poor prognosis. Only 1% get that far.
Archimedes in 2012 found 3 RCTs of steroids, treatment courses 2-4 weeks, seemed to shorten duration of abdominal pain, with most obvious effect when used early.
Dudley trial of early steroids (day 7) failed to find any benefit at 12 months (n=352). Quite a high proportion of drop outs unfortunately, but prob not enough to influence results. Doesn’t answer question of what to do if severe disease at onset eg nephrotic range. [Arch Dis Child. 2013 Oct;98(10):756-63.]
Non-randomized prospective clinical trial of 223 kids showed that steroids were effective in reducing the severity of abdominal and joint pain and in treating renal disease – steroids did not prevent the development of nephritis [Archives of disease in childhood. 2010;95:877–82, doi: 10.1136/adc.2009.182394 ]. Previous systematic review suggested that steroid treatment at diagnosis did not reduce the median time to resolution of abdominal pain but did significantly reduce the mean resolution time, and increased the odds of resolution within 24 hours.
There is no proven benefit of corticosteroids in the treatment of established HSP nephritis (2009 Zaffanello systematic review, evidence is poor), but used anyway.
The major risks of corticosteroid treatment in children with HSP are masking an acute abdomen or intussuception, and GI bleeding.
UK Kidney association guideline 2022 – for uncomplicated presentation, do frequent dipstick checks, for example weekly for first 4-6 weeks then monthly. BP check at presentation and then if evidence of nephritis. No need for parents to check at home otherwise. 6 months minimum (audit criteria, rather than recommendation).
If hypertensive or urinalysis pos, then do proper urine protein:creatinine ratio, U&Es, MC&S. Isolated haematuria is benign. As soon as urinalysis becomes normal, child can have routine follow up.
Scottish guideline was that persisting proteinuria of + or more needs more frequent follow up eg 2 weekly, 2 monthly then 3 monthly with the second line investigations.
Refer urgently for confirmed hypertension, or nephrotic range proteinuria (P:CR over 200mg/mmol).
Refer for biopsy if persisting severe proteinuria (UP: UC >250 mg/mmol for up to 4
weeks), persisting moderate proteinuria (UP: UC 100–250 mg/mmol for 3 months),
AKI stage 1 or greater (creatinine >1.5 × previous baseline or >1.5 × upper limit of normal for age). Treatment depends on histology and severity of clinical features.
ACE inhibitor is suggested (grade 2 recommendation) for persisting mild/moderate proteinuria.
A systematic review found no risk of long-term renal impairment in children with Henoch-Schonlein purpura with normal or minimal urinary findings without nephritic or nephrotic syndrome or renal failure (Arch Dis Child 2005;90:916-20). If urine analysis is normal at presentation, then test for 6 months after the last symptoms. If there is renal disease at presentation, then the risk for progression seems to be more associated with rising proteinuria during follow-up rather than presentation features. (Am J Kidney Dis 2006;47:993-1003)
Clinical picture, whereby kidneys leak protein, leading to hypoalbuminaemia. This results in oedema, particularly noticeable around the eyes, but also peripherally and as ascites. Mechanism is thought to be loss of negative charge on basement membrane. Usually idiopathic, mostly Minimal change glomerulonephritis. Otherwise can be focal segmental gomerulosclerosis (10-20%), secondary (eg HSP, SLE).
Mostly boys, 2 to 1 ratio. 5% go on to Chronic Renal Failure. Hypertension unusual so consider non minimal change glomerulonephritis if hypertensive at presentation. Classic features are:
Check FBC, U&Es, creat, albumin, LFTs, varicella IgG (to check status before starting steroids), cholesterol, HBV/HCV, C3/4. Urinalysis, urine culture, protein:creatinine ratio. Urine sodium <10mmol/l indicates hypovolaemia.
Those with minimal change tend to be responsive to steroids and do not need a biopsy. But if atypical or unresponsive (allow 4 weeks) then biopsy indicated; or if:
Remission defined as 3 consecutive days neg or trace protein. Most remit within 1 month, refer if no response by then – allow 8/52 before labelling steroid resistant .
1/3 no relapse, 1/3 infrequent, 1/3 frequent. Nephrotic relapse defined as 3+ protein for 3 days, but also refer if 2+ for 7 days. Treat relapse with prednisolone 2mg/kg until proteinuria suppressed for 3 days, then taper over 4-8 weeks. In frequent relapsers (ie 2+ within first 6 months, or 4+ within any 12 month period), may become steroid dependent (ie relapses during weaning) so consider Levamisole (2.5mg/kg alternate days, SE reversible neutropenia), cyclophosphamide, ciclosporin etc.
As with any condition requiring high dose steroids, remember vaccinations, varicella, bones.
Children with steroid-resistant nephrotic syndrome who are homozygous or compound heterozygous for NPHS2 (podocin) mutations do not respond to standard steroid treatment and have a reduced risk for recurrence of nephrotic syndrome (with focal segmental glomerulosclerosis) after renal transplantation. Available through UK Genetic Testing Network for children with nephrotic syndrome that is resistant to treatment with steroids, presents in the first 3 months of life or has a histological picture of focal segmental glomerulosclerosis on renal biopsy.
See also:
A common, potentially serious, infection in children. More common in girls over the age of 3 months, more common in boys below that.
Generally occurs by ascending infection from urethra. Most common organisms are E coli, Klebsiella, Enterococcus faecalis, Proteus. Infection appears to develop clinically when bacteria in the urine manage to adhere, hence depends on presence of fimbriae on bacterium, and ability of urothelium to resist adhesion (genetic factors).
Classic symptoms are of cystitis:
There may be systemic features, eg fever, nausea/vomiting, lethargy. However these are more common if the infection progresses to pyelonephritis:
Besides the inconvenience, particularly or recurrent cystitis, there is also the risk of long term kidney damage (chronic pyelonephritis, with renal scarring).
Immunodeficiencies rarely increase risk of UTI, neutrophil disorders are perhaps the exception.
Besides septicaemia, the major complication of concern is renal scarring, with potential for long term chronic pyelonephritis and premature renal failure.
Risk factors are: (n=1280)
Having 2 or more of the first 3 puts you in a high risk group with double the overall risk of scarring (30 vs 15% in this study). Covers 21% of the total sample. Sensitivity is so-so: catches 44.9% of all scarring.
Adding in bloods and/or a micturating cystourethrogram (MCUG) only increases the predictive value by 3-5%. [JAMA Pediatrics. 168(10):893-900, 2014 Oct. PMID: 25089634]
There are many studies showing that scars can develop without reflux, and that many children with reflux (but without infections) do not develop scars. Scars are associated also with delayed treatment. Cochrane review did not come out strongly in favour of identifying VUR – nine reimplantations would be required to prevent just one febrile UTI, with no reduction at all in the number of children developing any UTI or renal damage. Archives, 2003
What is the risk of long term damage? Low, given that UTI is common, the occurrence of CRF is rare, and acute pyelonephritis with severe long term complications is also rare. The only large population-based study (n= 1221) found a low risk of hypertension after 16-26 years: only 9% of children with scarred kidneys became hypertensive cf 6% for unscarred. Glomerular filtration rate in later life was normal in both those with and without scarring. Archives of Disease in Childhood 2007;92:357-361
Apart from addressing risk factors, you need to consider looking for underlying VUR or else evidence of renal scarring. See NICE CG54 guidelines. For Scotland, see SPRUN guidelines.