See also UTI, HSP, Urine testing, Urology.
GFR - usually measured by protein:creatinine ratio. Can be done from a spot urine but note there is diurnal variation so best done in the morning. Albumin:creatinine ratio is probably better, and cheaper.
See Urine testing.
One off episode seen in 4% of normal children. Only 1% positive twice. Asympt recurrent can be monitored for 5yr!
Beware:
First: Red cells or not? (myoglobinuria = haemolysis, beetroot! Porphyrins, other unusual pigments). Nephritis or not? (proteinuria)
Urine calcium/creatinine has age specific normals, but over 0.6 is abnormal, especially in the presence of a normal plasma calcium
Do FBC, creatinine, USS, 24 hour urine calcium/creatinine, culture, C3. Consider poststreptococcal (ASOT, throat swab), SLE, sickle cell, coagulopathy, stones (urine Ca/creat, Oxalate/creat. Urate. pH. Vit D metabolites. KUB).
Differential is:
Biopsy if persistent high grade microscopic, or microscopic with proteinuria (>150 mg/24 hr)/hypertension/impaired renal function, or 2 episodes of gross haematuria. Cystoscopy for bladder problem.
Normal range depends on age and height - see Peds 1996;98:649.
Moderate = consistently above 95th centile but no end organ damage. Severe is 10-20mmHg above 95th centile PLUS end organ damage.
Causes:
Secondary investigations are more directed:
Strong genetic influence, through eg angiotensin receptors, uroplakin genes.
HUS is triad of microangiopathic haemolytic anaemia, thrombocytopenia, and acute nephropathy. In kids 90% are post colitis (D+ HUS), due to Shiga toxin (Stx) producing E. coli (esp O157:H7). Some children carry O157 without becoming symptomatic; otherwise symptoms develop 3-7 days (mean, range up to 12 days) after ingestion of the bug. Starts with an unremarkable diarrhoeal illness for the first 1-3/7, 90% then go on to have colitis. Fever often reported but rarely present at presentation, unlike other infectious causes. Abdominal pain is usually severe, and there can be abdominal tenderness and pain on defecation.
Only 15% of those who get colitis go on to get HUS; not all develop acute renal failure, some only get haematuria and proteinuria. Onset of HUS is median 7 days (range 5-13 days) after onset of diarrhoeal symptoms. The risk period appears to be over once the platelet count stabilizes or begins to recover, and symptoms are resolving.
Enterohemorrhagic E. coli (EHEC) produce AB toxins (single A subunit surrounded by five B subunits). Carried by cattle, sheep as well as wild (eg deer, seagulls) fauna as well as humans. 39% of cattle farms found to have O157. Outbreaks often related to contamination of non-meat products eg drinking water, raw vegetables/salad, dairy products. Very low infectious dose viz probably under 1000 organisms hence potential for outbreaks. Ones that produce shiga-like toxins are called VTEC (verotoxin is another name for shiga toxin), not all O157:H7. Ingestion of EHEC causes colitis, facilitating transmural absorption of toxins (lipopolysaccharide probably important too) into the circulation. The toxins then bind glycoprotein (Gb3) receptors on target cells in the gut, kidney, and occasionally other vital organs (variable expression). Results in damage to cells and detachment from their basement membranes, then secondary activation of platelets and the coagulation cascade.
0157:H7 has lots of virulence factors, plus hardy. Viable disease producing E. coli have been found in environments up to 10 months following initial contamination.
10% of cases labelled as atypical (D-) HUS, who tend to have no diarrhoea, recurrent disease, and poorer prognosis. Other organisms, drugs, and conditions implicated: causal or association?
Ask about contact with farms or farm animals. May look anaemic or have petechiae. Check Hb, platelets, film, LDH, VTEC serology (at day 5, more sensitive than culture), urinalysis. Important to notify lab of suspicion, considering rapid disease progression, should be plated out immediately rather than the following morning. Fastest diagnostic test is Sorbitol MacConkey (SMAC) culture, growing colourless ie non sorbitol fermenting cf usual pink colonies (85% specific). Then use O157 antiserum or latex reagent to confirm the diagnosis. Antigen tests for toxin are overnight tests, and good for identifying non O157 VTEC (80%! Clinical Microbiology & Infection 14(5), 2008, 437–445) but they do not help isolate the actual organism for public health lab uses, and are not 100% sens. Best done on growth from culture rather than the original sample. So use both culture and antigen test to maximize sensitivity.
CDC recommends O157 culture and shiga toxin testing on all community acquired diarrhoea. Enhances ability to monitor outbreaks if strains identified as early as possible. Late in the illness eg after 1 week the sensitivity of testing decreases (even toxin genes may be lost).
Sorbitol fermenting strains described. PCR tests for stx genes used by reference labs.
Management is supportive. Asymptomatic cases do not need bloods (letter, Archives 2008 pmid 18208996), but ongoing diarrhoea in well children must be closely monitored (development of HUS may occur without frank colitis). Facial pallor predicted HUS in 1 study; oliguria, proteinuria and haematuria, rising LDH are diagnostic, rather than predictive of HUS (OR 6-17) (Pediatr Int. 2009 Apr;51(2):216-9 PMID 19405919). although interestingly these features generally appear before red cell fragments on film! Fever was the only significant risk factor for HUS from history in the first 3 days of illness in 1 study, but poor PPV (Ikeda, Epid infection 2000; 124:343). High early WCC (>12) has 89% sensitivity and 99.5% specificity (Archimedes, Arch Dis Child 2007). Raised CRP also predicts HUS (Ikeda, as before, who propose scoring system of 2+ features of fever, CRP and WCC - 32% sens cf 98% spec).
Median time for development of HUS from onset of symptoms is 9 days (range 1-15 days).
A rising lactate dehydrogenase of >1200 IU/L per day (OR = 26.3) and creatinine >0.5 mg/dL per day (OR = 12) predict neurological complications (Pediatrics International. 51(2):216-9, 2009 PMID: 19405919). SCWP score (sodium, CRP, white blood cell count, and total protein) has been suggested (Pediatrics International. 51(1):107-9, 2009 PMID 19371288).
Plasma exchange should be considered for cerebral involvement or metabolic derangement as well as renal failure. Consider also for Factor H or vWF cleaving protease deficiency. Definitive therapy for factor H deficiency has been a liver transplant (the site of factor H production).
Platelet recovery comes first. Infection control necessary until 2x negative stools. Carriage is usually transient.
The most promising preventive measure for those who have colitis but have not yet shown signs of HUS is monoclonal antibodies vs Shiga toxins during the 3 to 5 day window prior to onset of HUS. Requires rapid detection test. Otherwise, potential for interrupting pathogenic cascade?
Although about one half of patients with D+ HUS require a period of dialysis, mortality rate is now down to 3 to 5%. Even so, some patients develop life-threatening extra-renal complications.
30 to 50% of those surviving the acute phase of D+HUS will have signs of kidney damage and/or hypertension. Some who experienced pancreatic damage acutely later develop insulin dependent diabetes. Those with proteinuria (+/- impaired glomerular filtration rate) are probably suffering from hyperfiltration injury that can progress to eventual end-stage renal disease.
There is evidence that the HUS population (like others with renal damage) benefit from ACE inhibitors as they slow the progression of hyperfiltration injury. Recurrence rate in transplanted kidneys for D+ HUS is low - those with atypical HUS have much higher recurrence risk.
CurrOp Peds Volume 17(2), April 2005, pp 200-204
HUS does not have long lasting neurological effects as long as patients have no obvious neurological problem at discharge (Arch).
Emphasis on prevention eg safer slaughterhouse, meat processing, food handling and cooking standards.
After infection: multivariate analysis suggests that onset of renal failure is inversely associated with amount of IV fluid and sodium infused - could generous IV saline administration on presentation with bloody diarrhoea prevent onset of renal failure? Pediatrics. 2005 Jun;115(6):e673-80.
Isolation: secondary cases of O157 colitis are seen in about 20% of cases - about half of these are siblings. The risk of a secondary case is higher if the index case is under 5yrs. The risk of HUS is about the same viz 25%. Isolating patients who were aged under 10 years and who had a sibling gave a NNT to prevent 1 case of HUS of 47 (95% CI 16-78).Clin Infect Dis. 2008 PMID 18444854
No evidence that excluding carriers from work or school settings is effective!
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.
Problems:
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:
Should respond to steroids within 1 month else refer.
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. Statins?
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.
Syndrome of oliguria, haematuria (?microscopic) and hypertension. If severe leads to fluid overload eg pulmonary oedema.
Check:
Causes:
C3 low in all GN, low C4 in membranoprolif, SLE, SBE, shunt nephritis.
Occurs 2/52 post pharyngitis, 6/52 post skin infection. Proteinuria/haematuria persist for 6/12. ASOT should be positive, otherwise anti DNAse B is another streptococcal test. Monitor blood pressure and GFR.
NSAIDs with hypovolamia predispose to renal failure because prostaglandins mediate cardiovascular compensation via renin etc.
Other nephrotoxic drugs - vincristine, cyclophosphamide, methotrexate, aminoglycosides (can occur with normal levels, normal urinalysis! Related to dose & duration), aciclovir (crystals), radiological contrast.
Other factors/causes:
To differentiate -
To calculate Fractional excretion: you want to know what percentage of the expected sodium in the urine (on the basis of concentrating ability) is actually excreted (in other words, successfully retained). Calculate the renal concentrating ability by dividing urine creatinine (usually reported in mmol) by plasma creatinine (usually reported in micromol). You would expect the sodium loss to be that amount times plasma sodium. But you only get a fraction of that; so divide the actual urine sodium by the expected value to get a percentage.
Insensible losses 25ml/kg under 10kg, 15ml/kg 10-20kg, 5ml/kg if 20+kg.
For hypocal, 50mg/kg/d oral calcium.
Nutrition is significantly associated with outcome in ARF. Enteral, no protein restriction unlike adults, but high bioavailability preferred. Filter if necessay to achieve volume.
Renal replacement for hyperkalaemia, refractory acidosis, fluid overload, encephalopathy.
Various kinds of leakiness, various causes. Main groups are the renal tubular acidoses:
Fanconi syndrome - phosphaturia, glycosuria, aminoaciduria, proteinuria. Ricketts and osteomalacia are the main complication.
Cystinosis is an autosomal recessive condition leading to Fanconi syndrome in infancy. The corneas and thyroid can also be affected, causing photophobia and hypothyroidism. Treatment is with cysteamine and bicarb/citrate.
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