Renal And Urinary Tract

Renal & Urinary Tract Embryology Renal tract develops from cloaca and mesoderm Fetal excretion is via placenta Fetus has infinite supply of water & sodium (via placenta) therefore immature renal tubules lose Na and therefore H2O - Fetal urine is hypo-osmotic (230-660mls/day) With stress of birth (peripheral vasoconstriction, opening of pulmonary system) the GFR falls Relative oliguria for 1-2 days (while minimal intake from breast milk) Baby’s initial weight loss = Na & Water Na > 140 in first few days = lack of water (if excess Na intake = water retention) Low Na = SiADH, No solute in fluids (10% dextrose) or unbalances losses) Infants have lower HCO3- levels. GFR at term birth is 25mls/min (10-15mls/min if 31 wks) Increases after 1st 2/52 to 50mls/min Then over 2 years to adult levels ADH (aka vasopressin) A nonapeptide Produced in supraoptic / paraventricular nuclei of hypothalamus Released from posterior pituitary Acts mainly on collecting ducts à improve H2O permeability & increased H2O retention ALSO - in high concentrations à peripheral vasoconstriction à raises BP Carbemazepine, Thiazides & SSRIs can increase release Ethanol inhibits release Renal Function 120 x blood volume is filtered daily Proximal tubule Reabsorbs glucose, AA, PO4, Urate, Bicarb & CA Secretes Creatinine Loop of Henle > 50% of Na is reabsorbed by start of Distal tubule Distal tubule Reabsorbs Cl & H2O (under action of aldosterone) Secretes H+ Fractional excretion Fractional excretion of X (FE %) = (Urine X / Filtered X) x 100 Is valid if substance is NOT reabsorbed – But still used when it is FE Na = (Urine Na / Filtered Na) x 100 Urine Na = Urine conc x vol Filtered Na = GFR x plasma conc GFR = (Urine Cr/Plasma Cr) x vol THEREFORE e.g. Shock FE Na = Urine Na x vol x Plasma Cr FE Na = <1% = functioning tubules therefore pre-renal failure FE Na = >1% = ATN e.g. Hyponatraemia FE Na = < 1% = salt loss / increased water FE Na = >1% = renal salt wasting e.g. hypernatraemia FE Na = <1% = renal concentrating defect FE Na = > 1% = salt overload Imaging US – renal size + cysts Radioisotopes – to establish filtration function MAG3 – Inject isotope, uptake by kidneys. Can assess uptake, obstruction & use to give MCUG. Gives idea of renal flow but not accurate GFR. Allows plotting of excretion curves. DMSA – 90% is bound to plasma proteins therefore NOT filtered = images showing functioning tubules Good for showing scars Usually take posterior images (better pick up of radiation) therefore images are displayed wrong way around. CAN be taken anteriorly if … Transplanted kidney (= anterior location) Horseshoe kidney (= spine reduces view of isthmus) Pelvic kidney (sacrum in way) Outlines scarring or dysplasia (false +ve if shortly after UTI) MCUG – dye into bladder & observe reflux Instill contrast medium into bladder via catheter (or Supra-pubic puncture). Bladder will be full (in IVU = ½ full) Withdraw and take series of video images to demonstrate any reflux Plain XR – stones, L-Spine abnormalities. IVU if ?PUJ obstruction CT / MRI Urine Urine Output Proteinuria 2ml/kg/hr (infant), 1ml/kg/hr (toddler), 0.5ml/kg/hr (adult) Transient = common after febrile illness / exercise Postural / Orthostatic = Late in day (but not in 1st morning sample) – occurs in normal people Nephrotic Syn = heavy proteinuria with oedema Haematuria Microscopic = transient in many people Commonest in UTI (beware false +ves e.g. beetroot) Occurs in HSP, Wilms tumour, hydronephrosis & others Glycosuria & aminoaciduria due to ­ serum levels or tubular defects pH Should be 5-7 If < 5.2 then ? Renal tubular acidosis Can be due to lithium (à RTA & Nephrogenic DI) Osmolality 1st morning urine sample, normal > 800mOsm/kg Nitrites & Leucocytes indicate infection Haematuria >5rbc on freshly spun urine per high power field NB: beetroot / blackberry, rifampicin & urate crystals can cause false red If + protein = likely significant problem Physiological Idiopathic transient haematuria = common Exercise induced – resolves in 48 hrs Familial benign haematuria – usually asymptomatic Gross haematuria with +ve FH Can be benign / Alports / others Glomerular 1o post infection Glomerulonephritis (acute / chronic) Hereditary / familial nephropathy IgA nephropathy Non-glomerular UTI (bact / virus / TB / schistosoma) Stones Tumour (genital / renal / ureteric) Trauma – abdo / perineum Structural (e.g. cysts) Drugs (e.g. cyclophosphamide) Sickle Renal vein thrombosis Haemorrhagic cystitis Due to delayed presentation of UTI (e.g. in learning difficulties) Gross haematuria with clots Fever, suprapubic tenderness Psychosocial – fictitious Proteinuria Variable – orthostatic/postural, transient (fever, UTI, CCF) Orthostatic proteinuria Asymptomatic Protein loss higher on standing compared to lying down FU as prognosis is unclear Non variable glomerular 1o (post infection, glomerulonephritis) 2o to systemic disease, hereditary nephropathy, drugs (gold, penicilliamine), reflux, sickle cell Non variable, non glomerular – fanconi syndrome, ATN, structural, heavy metal poisoning Dehydration / hypovolaemia Generally decreased intra/extravascular compartment BUT in nephrotic syndrome à low albumin à oedema + hypovolaemia Clinical estimation of ECF vol deficit = based on Sx & Wt Mild = 3-5% loss à thirst, dry membranes, decreased skin turgor Mod = 5-10% loss à above + sunken AF, Sunken eyes & tachycardia Severe = 10-15% loss à above + drowsy/confusion/coma, shock, cool peripheries, prolonged CRT & low BP Treatment Usually low H2O = low Na therefore replace with 0.9% saline Aim to treat shock over 1-2 hours à correct full deficit over 24 hours IF hypernatraemic (Na>150) then aim to lower plasma Na over 24-48 hours Oedema Abnormal increase of interstitial fluid Localised – indicates venous/lymphatic drainage obstruction (e.g. turners, HSP, sickle cell, DVT) Generalised Renal – nephritic syn, acute glomerulonephritis, ARF, CRF Cardiac – CCF Hepatic –chronic liver disease, venous outflow obstruction Neonatal – extreme prem, perinatal asphyxia, hyaline membrane disease, haemolysis, congenital lymphoedema, turners, CF Urinary Tract Malformations Most unilateral & detected in-utero by USS after 22/40 Palpable bladder in male infants ALWAYS abnormal Renal pelvis dilatation – (>5mm) if seen on 20/40 scan then rescan at 32w. Seen in up to 2% of pregnancies. Mostly physiological. Can indicate obstruction (PUV / PUJ / Duplex system / Dysplasia / VUR) Oligohydramnios = sign of poor renal function / obstruction Renal Agenesis à oligohydramnios & compression of fetus (potters syn) Potter’s Syndrome – bilateral renal agenesis + dysmorphism 1/4000, m>f Severe lung hypoplasia Beaked nose, low set ears, prominent epicanthic folds, antimongoloid slant to eyes Fibrinoid necrosis to placenta Pseudo-potters - Polycystic kidneys and obstructive lesions Prune Belly Syndrome Majority (95%) male Triad Deficient abdo muscles Dilated, non-obstructed urinary tract Bilateral undescended testis 20% die from pulmonary hypoplasia 70% have reflux Develop end stage renal failure by late childhood Obstructive Uropathy Pelvi-ureteric Junction (PUJ) obstruction = commonest cause of hydronephrosis Occurs in 1st trimester More common in males, L>R, 25% bilateral If not found before birth, present as abdominal mass, vomiting, pain, haematuria and UTI Rx: pyeloplasty (or nephrectomy if function < 15%) Vesico-ureteric Junction (VUJ) obstruction à megaureter Rx: reimplant ureter to overcome obstruction Posterior Urethral Valves ONLY in males = Commonest cause of lower tract obstruction Membranes with eccentric opening à varying degree of obstruction Prostatic urethra dilates à detrusor & bladder hypertrophy à reflux & hydronephrosis If severe can be pulmonary hypoplasia Assoc with prune belly syn Proximal urethral obstruction (folds of mucosa = valves) à thickened bladder, trabeculations etc Dx: on USS (antenatal) or postnatal (distended bladder, poor stream - dribbling, uraemic) Management If mild à surgical resection via cystoscope Ureterocoele Expanded end of ureter usually at ectopic site on bladder Can à filling defects, prolapse into bladder & therefore mass felt in vagina Obstructs drainage from the affected side Dysplasia & Cystic Kidneys Abnormal development at the stage of metanephros. Histology shows primitive cells Multi-Cystic Dysplastic Kidney (MCDK) = most common 1/4000 live births, 90% unilateral, 25% have abnormality of other kidney e.g. PUJ obstruction Affected kidney is non-functioning & usually not connected to bladder No proven risk of tumour / hypertension if left Often involute if left alone, otherwise resect AD polycystic disease 1/200-1/1000 = commonest inherited renal disease Parents can be asymptomatic – usually presents in 3rd-5th decade Clinical spectrum from failure to incidental cyst Rx any HTN & Screen family for genes AR polycystic kidney disease (aka infantile) 1/6000 – 1/40,000 Can be diagnosed antenatally Liver & kidney cysts à masses = large & easily palpable Oligohydramnios à pulmonary hypoplasia à some cases fatal at birth Hepatic cysts can à fibrosis If survive often à failure in early childhood 50% 10 yr survival Mx – aggressive rx of HTN à Transplant Familial juvenile nephrolithiasis (AR) / medullary (AD) cystic disease Normal size kidneys FJN = early polyuria, polydipsia, renal insufficiency, anaemia, pigmentary retinopathy, hepatic fibrosis and skeletal abnormalities MCD = presents mostly as an adult as HTN, haematuria and proteinuria Structural variants Horseshoe kidney Lower pole further from midline can get PUJ obstruction à hydronephrosis Ureteric Duplication Ureter draining upper moiety drains to lower point of bladder & is longer so prone to blockage (often ends in uterocele), shorter is prone to reflux Bladder extrophy M>F Failure of midline fusion Sx – Small bladder, herniated through abdo wall, low umbilicus, pubic bones unfused, legs externally rotated Boys – epispadias, undesc tesis & deficient penis Girls – clitoris in 2 halves & duplicated vagina Rx: urinary diversion Urachal remnants Can à blind tracts in lower abdo wall or fistula to base of cord Renal Calculi Urolitiasis = stones Nephrocalcinosis = Ca in kidney parenchyma Rare in children so all require Ix ½ of stones in children are infective (proteus) If metabolic then usually 2o to hypercalcaemia S&S: haematuria, Flank/abdo/back pain, UTI (proteus) Rx: increased fluid intake, lithotripsy/surgery Ix Bloods - UE, Bone, Mg, Bicarb, Cl & PTH Imaging - AXR, US Urine – microscopy & biochem = Ca, Mg, oxalate, glycolate, glycerate, urate, cysteine:Cr, pH Causes Struvite = radio-opaque – assoc with UTI Ca = radio-opaque Increased urine Ca + normal blood Ca = idiopathic, distal RTA, furosemide, hyperalimentation, hypophosphataemia, juvenile RA, medullary sponge kidney Increased urine & increased blood Ca – hyperparathyroid, excess vit D Increased urine Ca & LMW proteinuria = Dents disease Oxalate stones – radio-opaque = 1o hyperaxaluria type 1 or 2, enteric hyperaxaluria, idiopathic Uric acid stones – radiolucent – familial, overproduction, hyperuricouria Cysteine stones – usually opaque – cysteinuria Urinary Tract Infections 8% of all girls in 0-10yrs, 1% of boys affected Only 1% incidence in neonates Any PROVEN infection > 105 colony forming units (103 if catheter, 103 Gr +ve or ANY Gr-ve if SPA) NEED investigation (esp. in preschool age) Squamous cells indicate likely contamination Organisms 75% are E.coli Others include enterococci, klebsiella, proteus and serratia Infants S&S: vomiting, diarrhoea, poor feeding, fever, jaundice, septicaemia Dysuria differentials Physiological – tight underwear, masturbation, inexperienced tampon use Pathological Dehydration - Concentrated urine Dermatitis – irritants, eczema, psoriasis Infection – UTI, vulvovaginitis, STI, worms, candida Sexual abuse Causes Perineal hygiene problem Poor fluid intake g>b Blood borne source Genetic – structural problem Instrumentation Voiding problem Ix: BP (renal damage) Microscopy & culture On urine sample - clean catch or SPA should be sterile, bag only significant if –ve, if systemic unwell also do full septic screen Lab culture = >105/ml Nitrite = 100% of +ve • 85% of growth is e.coli • Others = Klebsiella, proteus, strep faecalis • If abnormal urine tract = pseudomonas, s.aureus Renal USS (any time) but often misses small scars DMSA – small dose of ionising radiation. Detects scarring. Needs cannula. Do 2-5/12 after acute infection otherwise false uptake MCUG – ionising radiation to gonads. Demonstrates VUR + urethral anatomy. Needs catheter MAG3 – IV injection. High false –ve, no anatomical info but info on function AXR – stones & spinal defects Rx: ↑fluids, mild analgesia Abx (based on culture – usually trimethoprim, co-amox, nitrofurantoin or cephradine) Obtain sterile urine post Rx All proven infections require radiology to assess for malformations VUR persists in 30% of confirmed UTI (increased if FH of VUR) Complications Risk of reflux à pyelonephritis à renal scarring, ↑BP, end stage renal failure NB: recurrent infection + genital signs / Gonococcus = ? ABUSE Control of micturition: Requires… Compliant bladder for storage Working detrusor & sphincter control AND autonomic control for co-ordination Sympathetic NS à NA à stimulates contraction of neck & relaxation of detrusor Parasympathetic NS à ACh from S2-4 à detrusor contraction Potty training recruits supraspinal polysynaptic reflexes to bring process of inhibition & simulation to voluntary control Enuresis By 6-12m voiding is less frequent due to CNS inhibition By 2yrs have perception of “fullness” Most children are dry by 3 yrs (day) and 5 yrs (night) Causes for concern Daytime Sx & enuresis by 4yrs (2-4% will have enuresis at puberty) 2o enuresis at any age (is almost always psychological) Causes of Wetting Physiological Maturation – 1o enuresis Inattention to need to void (b>g) Giggle incontinence Pathological Neurological – detrusor hyperreflexia Bladder Dysfunction – 1o instability, 2o instability, urge Congenital malformation – spinal problem, Posterior urethral valves Genetics – hereditary enuresis Psychosocial – anxiety, bullying, sexual abuse Nocturnal enuresis Wetting > 1 / wk after 5 yrs old 10-15% of 5 yrs B > G, +ve FH (75% if both parents) Increased if social disadvantage, learning problems or first born Exclude DI, DM and UTI History Exam (abdo, limbs, spine etc) Rx: +ve support & rewards Decrease late night fluid Pre-empt by waking child Desmopressin (ADH) = 50-80% successful but high relapse rate. Best used sparingly for holidays etc Enuresis alarms Day wetting Isolated 1%. (1.5% have combined day & night) Urge = commonest - 50% have UTI Stress = rare Transient =with UTI Careless = insufficient voiding time / emotional disturbance Rx: aggressively Rx of infections & constipation. Regular toileting etc Neurogenic Bladder E.g. due to meningomyelocele / sacral agenesis etc Lack of co-ordination between bladder & sphincter à functional outlet obstruction à increased pressure à VUR à scarring If bladder is atonic/ denervated sphincters then lower pressure but stasis à UTI Rx: Should be catheterised (intermittently) & on prophylaxis Vesicoureteric reflux Retrograde flow from bladder 1% incidence (if +ve FH in 1st deg relative then 20-50% risk) 30% of children with UTI Usually congenital à renal scarring (due to immune reaction & inflammation) à decreased renal function, growth failure, HTN & PIH risk. Also risk of UTI Likely AD inheritance with variable penetrance (high rates in sibs). Can à scaring and ascending UTIs Grading 1. Normal ureter calibre, partial reflux 2. Normal calibre, reflux to pelvis 3. Slightly dilated ureter, clubbed calyces 4. Marked dilatation with clubbed calyces 5. Severe dilatation with effacement of calyces Treatment Abx until resolution for all groups 1&2 à 80% resolve with age à antibiotics (trimethoprim 2mg/kg). 3 à Teflon inject to improve valve STING (endoscopic subureteric injection) = inject tissue augmenting substance under GA. Can be done as day-case/ short stay 4&5 à <20% resolve in 5 yrs àureteric re-implantation (95% success) & if other kidney normal à partial/total nephrectomy Polyuria > 1 litres preschool, > 2 litres school age, > 3 litres adolescents Is assoc with polydipsia if not causing dehydration Causes Physiological – excess intake (esp caffeine), excess salt load (poisoning) Pathological – Endocrine - DM / DI Chronic illness – nephrogenic DI, Renal failure, concentrating defect Genetic – sickle Psychogenic Pharmacological = diuretic Ix: Baseline plasma electrolytes, glucose, Ca, sickle screen, US renal tract If normal try water deprivation test (+ DDAVP) and recheck MRI posterior pituitary (? Insuff ADH) Diabetes Insipidus Polyuria & polydipsia in the absence of osmotic diuresis High serum sodium Low urine osmolality (< 200 MOsmols/kg) SG of urine < 1.005 Other features Hyperthermia Cravings for water & ice cold drinks Growth failure – poor calories & excess H2 Mental impairment – due to recurrent hypernatraemia Central = problem with ADH secretion (U.osmo > 800/kg after deprivation test) Rx with ADH Nephrogenic = unable to respond to ADH à concentrating defect Congenital = most severe Familial form is X linked à mostly in males, occasional in female sibs Presentin newborn period with dehydration, poor growth and irritable Can occur in chronic renal insufficiency, lithium toxicity, hypercalcaemia, hypokalaemia Poor feeding, FTT, rapid onset of dehydration with illness / hot environment / water shortage Short stature High urine volumes à dilatation of ureters & bladder High Serum Na, low urine osmo (<200) & low urine specific gravity Serum ADH = normal / raised Unchanged Osmo after water deprivation test RX with thiazides, dietary salt restriction & Indometacin (to reduce renal blood flow à reduce GFR) Nephrotic Syndrome Peak 2-6yrs, b>g 5/100,000 / yr = (1/6000 total)(↑ in Asians), Pathophysiology Increased glomerular capillary permeability à protein loss (mainly albumin) Infection - most commonly s.pneumonia / gr -ves Ig loss – less able to handle bacteria Oedema (increased risk of peritonitis) à reduced circulating volume à RAA system à sodium & water retention. Steroids (may mask Sx) Triad of 1. Proteinuria 2. Hypoproteinaemia à Oedema Albumin < 20g/l à net movement of fluid à pitting oedema & effusions & decreased UO 3. Hyperlipidaemia (Increased cholesterol & TG) (+/- haematuria (10-20%), HTN and decreased GFR) S&S: Periorbital & dependent oedema, abdominal ascities, pain, D+V, hypovolaemia & risk of circulatory collapse (fluid leaves vascular compartment) à ARF, ↑ risk of thrombosis, skin breakdown due to oedema Ix Bloods - UE, Bone, LFT, Lipis, C3/4, ASOT, ANA, Auto Ab screen, Hep B & varicella, FBC Urine - Urine osmo, Pro:creat ratio Biopsy if… <1yr / >10yrs, gradual onset oedema, macroscopic haematuria, HTN, rash/fever/systemic upset, low C3/4, Failure to respond to steroids by 4/52 Types 90% are idiopathic 85% = minimal change - normal glomerulus, negative IF, normal BP 95% of these will respond to steroids 10% = focal sclerosis - scaring in juxtamedullary region 5% = mesangial proliferation - increased mesangial cells, IgM & C3 on IF. More common in older children 10% are 2o to glomerular nephritis (most commonly membranous or membranoproliferative) Causes: Infection (malaria or often occurs post viral) Poisons (mercury) Allergies (bee sting) Collagen vascular disorder (SLE) Renal vein thrombosis Prognostic factors Minimal change = best prognosis. Especially those with loss of >2g protein in 24 hours of mostly albumin Worse prognosis associated with HTN and/or macroscopic haematuria (assoc with nephritic syndrome) Rx: monitor pulse, BP, weight & haematocrit, Give 20% IV albumin to improve hypovolaemia (pulls fluid back to vessels) STEROIDS - Pred 60mg/m2 for 4/52 fb 40mg/m2 alt days Ascitic tap for MC&S (↑ risk of peritonitis) Fluid restrict if oedematous, otherwise sodium restrict Prophylactic penicillin to prevent pnumococcal peritonitis If no response to steroids à biopsy Prognosis In children will often relapse, but usually resolved by 20yrs Congenital nephrotic syndrome AR Sx - Proteinuria at birth, Antenatal raised AFP, Premature BUT tendency to meconium, Large placenta, Resp distress, Separation of cranial sutures Dilatation of the proximal convoluted tubules = microcystic disease on biopsy Present before 3 months old with oedema, recurrent infections and death by 5 years if no treatment is available. Treatment is with ACEi’s to control BP, albumin infusions à partial medical nephrectomy (indomethacin to reduce GFR) à nephrectomy & dialysis à transplant No response to steroids Analgesic nephropathy 2o to prolonged analgesia use (e.g. NSAIDs) – can also be sulphonamides or methicillin Interstitial nephritis +/- capillary necrosis à renal concentrating defect Glomerular disease All have proteinuria But not all proteinuria is glomerular disease (can be transient with illness, UTI, surgery, trauma, physiological (more common if upright/exercise)) Proteinuria + oedema /HTN/Oliguria = EMERGENCY Glomerular disease can à nephrotic syndrome, acute GN, rapidly progressive GN, chronic progressive GN or asymptomatic proteinuria/haematuria Glomerulonephritis Haematuria & Proteinuria + Oedema +/- HTN IgA Nephritis is most common Ix – FBC, UE, LFT, Bone, Ig levels, C3/4, ANCA, Anti ds DNS Ab, Anti GMB Ab, Auto Ab screen, ASOT, Hep B&C, Urine Na, osmo, Cr & casts + Pro:creat ratio, Throat swab (streps), biopsy if unsure Specialist centre if high or increasing CR, oliguria, heavy/persistent proteinuria, severe HTN or severe oedema Acute Nephritic Syndrome Blood AND Protein in urine Post-streptococcal glomerulonephritis (e.g. 14 days post throat infect) Haematuria, oliguria, oedema Raised BP S&S: Many asymptomatic Malaise, headache, loin discomfort Smoky urine Periorbital oedema, oedema of hand & feet, Ix: Urine - haematuria, proteinuria, oliguria (if severe à HT, encephalopathy, seizures) ASOT (anti-streptinolysin titres) & anti DNAase B with Low C3 Rx: 10 days penicillin – little effect on recovery or spread Admit if oliguria (à salt restrict and balance fluid output), HT (à hypotensives) or fluid overload (à diuretics or peritoneal dialysis if severe with ↑K+). GFR should normalise in 10-14 days 95% have total recovery Henoch Schonlein Purpura (HSP) IgA mediated leucocytoclastic vasculitis = IgA nephropathy Features Purpura – NOT thrombocytopenic – on elbows, shins & buttocks Arthralgia (60%) Glomerulonephritis (membroproliferative) – blood & protein in urine 70% of HSP have haematuria or proteinuria, but usually asymptomatic (no pain) Oedema – to hands, feet, scalp, ears & scrotum GI bleed (>50%), abdominal pain, intussusception Histology Mesangial deposits of IgA (aldo IgM, IgG & C3) Thickened BM Ix – NORMAL FBC & Coag Biopsy à IgA mesangial deposition & occasional IgM/C3/fibrin HSP + Acute Nephritic Syn = BAD! – symptomatic management Prognosis Usually settles in 4-6 weeks if mild Can relapse Can have persisting nephrotic syndrome Bad prognosis if heavy proteinuria, oedema, HTN or decreased renal function <1% à persisting renal disease <0.1% à severe renal disease Management Observation only UNLESS CNS/severe gastro involvement (à steroids) Long term FU is mandatory Glomerulonephritis + pulmonary haemorrhage Goodpastures disease – Ab to lung & kidney BM (a.k.a. anti basement membrane disease) Goodpastures syndrome = same effect but other causes SLE, HSP, Polyarteritis nodosa, Wegners, Pulmonary haemorsiderosis Usually occurs in adolescent males Fe def anaemia Clubbing if long standing Pulmonary infiltrates on CXR (alveolar bleeding) Diagnosis by lung / renal biopsy Treatment = steroids + immune suppressive agents (azathioprine, cyclophosphamide, methotrexate) Membranous glomerulonephritis Rare in childhood, common in adults Immune complex mediated Diffuse thickening of GBM with granular deposits of IgG & C3 Onset in 2nd decade as nephrotic syndrome with microscopic haematuria (occasionally gross haematuria) Normal BP & serum C3 levels Causes - SLE, Cancer, Gold, Penicillin, Syphilis, HepB Increased risk of renal vein thrombus Usually resolves spontaneously Rx – salt restriction and diuretics Hypertension Persistent systemic HTN à heart failure, MI & stroke Obesity = contributing factor Kidney can be cause / victim Renovascular HTN = 5-25% of childhood HTN Due to Renin-angiotensin system with fibromuscular dysplasia Assoc with idiopathic hypercalcaemia, marfans, vasculitis, UAC use and abdo radiation Reflux nephropathy Usually > 5yrs 10% with scars have HTN Also seen in HUS, AR PCKD & AD PCKD Other causes inc Coarctation, Drugs, meds & poisonings Initial Ix UE, FBC, Renin & aldosterone levels, urine dip, urine catecholamines & metabolites, CXR, ECG, ECHO, Abdo US & DMSA Rx If mild – observe If severe – Ca blockers, ACEi’s, B blockers & vasodilators Acute Tubular Necrosis Can be caused by shock (high metabolic rate) / toxins (e.g. free Hb, antifreeze) Ix Blood urea : creatinine ratio of 10-20 Urine SG < 1.010 U.Osmo < 350mosmo/kg Urine Na > 40mmol/l Prognosis Cells will regenerate if insult removed Acute Renal Failure / Dysfunction Suspect in any oliguric patient Can be increased, normal or low UO Sudden drop in renal function à retention of N2 waste + fluid & electrolyte imbalance (acidosis, high K+ & PO4) & Oliguria (< 1ml/kg/hr in infant, <0.5ml/kg/hr in child) Causes Pre-renal – hypovolaemia– sepsis, trauma, burns, nephrotic syndrome, cardiac failure Renal – HUS, ATN, ischaemia, GN, pyelonephritis, acute interstitial nephritis, cortical/meduallary necrosis, bilateral renal artery thrombosis, infiltration by neoplasm Post-renal – bladder outflow obstruction, bilateral ureteric obstruction, stones, unilateral obstruction of single kidney, stones, neuropathuic bladder, trauma, tumour Rx: exclude obstruction with USS. Treat cause & give supportive Rx Excess water – trial of diuretics – response indicates pre-renal High calorie low protein feed Hyponatraemia à fluid restrict Hypernatraemia à salt restrict Hyperkalaemia à salbutamol & diet restrict (check ECG) Metabolic acidosis à cautious use of sodium bicarb May require RRT if: Anuria Urea > 35 CR > 400 K+ > 6.5 Fluid overload Metabolic acidosis Na < 110 or > 160 Ureamic complications Haemolytic Ureamic Syndrome = ARF + haemolytic anaemia + thrombocytopenia Commonest cause of ARF in children Caused by Verocytotoxin producing E.coli 0157 S&S: Mostly diarrhoea prodrome (if no diarrhoea = worse prognosis) Bloody diarrhoea for days to weeks Then decreased urine output, pallor & malaise D +V, pallor, haematuria, oliguria, seizures Ix: Microangiopathic haemolytic anaemia, low plts & renal failure Rx: Supportive - aim to correct ion balance, pH & haematocrit If pre-renal à urgent vol expansion, renal à IV frusemide / dialysis à good prognosis Chronic Renal Failure Sx Insidious onset - Often asymptomatic until 60-80% function lost = GFR < 50 mls/min/1.73m2 Poor growth (Protein-Calorie imbalance, renal osteodystrophy, Anorexia, acidosis, anaemia, salt & fluid loss) à give calorie & vitamin supplements, growth hormone & early dialysis Renal Osteodystrophy Initial stages à decreased renal excretion of PO4 à hyperphoshpataemia à reciprocal hypocalcaemia à osteomalacia à secondary hyperparathyroidism à bone reabsorption à osteoporosis Decreased 1,25 dihydroxycholecalciferol due to renal insufficiency High ALP Acidosis Chronic renal disease à altered skeletal growth & remodelling Visceral Calcification Usually due to progressive loss of nephrons Later sx à muscle weakness, bone pain, deformity, metastatic calcification, pruritis, frontal bossing, dental problems X-rays show subperiosteal erosion of mid & distal phalanges Rx – control PO4 (binders), increased Ca intake, extra vitamin D Anaemia (poor nutrition, ↓EPO, blood loss, decreased plt function) à EPO, Fe Supplements, Folic Acid Hypertension (Na retention, rennin release, renal disease à hyperfiltration) à Na restrict, diuretics, hypotensives, partial nephrectomy of non-functioning tissue. Controlling BP improves GFR Uraemia à convulsions, coma, flapping tremor, myocarditis & pericarditis Hyperkalaemia (due to increased aldosterone) Neuro – increased ammonia & accumulating Aluminium à fatigue, poor concentration, memory loss, slurred speech, muscle weakness End stage at < 10 mls/min/m2 Causes Children <5 yrs = structural Children >5yrs = acquired / hereditary Common causes include glomerulonephritis, pyelonephritis, hereditary nephropathies, congenital hypo/dysplasia and HUS Rx: EPO, ACEi, nutritional support, RRT EPO – side effects HTN & Seizures (warning prodrome of stabbing migraine headache) Increased K+ if already uraemic Raised PCV & Thrombocythaemia à thrombosis Induction of Fe def anaemia Skin rashes Urticaria Flu-like illness Peritoneal dialysis Indications Acute renal failure (esp HUS) Increase Na & K Increased ammonia / Maple Syrup Urine Disease Drug overdose (e.g. theophyline (no use for aspirin)) Renal tubular acidosis Distal = Type 1 Deficiency of H+ secretion by distal tubule & collecting duct Up to 10% of filtered bicarb lost in urine Urine pH > 5.8 despite systemic acidosis Loss of HCO3 à increase Cl & decreased K Proximal = Type 2 Partial defect in secration of H+ in proximal renal tubule & Associated reduction in reabsorption of HCO3 from the tubule à increased HCO3 to distal tubules à distal tubule unable to absorb it à Loss of upto 25% of filtered bicarb in urine Excessive loss of HCO3, AA, Glucose, Calcium, Phosphate and Potassium in urine Causes include cystinosis, Lowe’s Syn, Galactosaemia, Hereditary fructose intolerance, tyrosinaemia, Wilsons, Medullary cystic disease, acetazolamide, Fanconi syndrome, nephritic syndrome, renal transplant Presentation: FTT, Growth failure, Vomiting, dehydration, lethargy Ix: ABG shows normal anion gap MET ACIDOSIS Decreased serum bicarb Urine pH low (usually >5.5) Management: High dose bicarb supplement, treat rickets wth Vit D & PO4 supplements, monitor for low K Mineralocorticoid deficiency = type 4 Due to addisons / CAH / primary hypoaldosteronism Normal renal function Na wasting, High Cl & K+ Increased renin level NB – type 3 turned out to be a subtype of type 1 Fanconi syndrome Form of Type II RTA Disturbance of proximal renal tubule function but well preserved glomerular function Glucose, AA, Uric acid, Phosphate, Bicarb are NOT reabsorbed in proximal tubule à Overloaded absorption in distal tubule à excretion in urine of Na, Bicarb, PO4, glucose & amino-acids Loss of bicarb à Type 2 renal tubular acidosis Loss of Phosphate à rickets Sx - Growth retardation, polyuria, rickets, metabolic acidosis (with normal anion gap), decreased PO4 & K+, amino acid uria Low NA, K, bicarb & PO4 MOST have fair hair, blue eyes Causes Genetic – galactosaemia, mitochondrial, cystinosis, lowes’s syndrome, wilsons Acquired – drugs (aminoglycosides, ifosfamide), renal disorders (ATN recovery, early posttransplant, interstitial nephritis), Others – heavy metal poisoning / multiple myeloma Rx: elimination of cause (avoid AA etc) + supportive (vit D supplements) Lowes syndrome (oculocerebrorenal dystrophy) XLR Occulo - Congenital cataracts, glaucoma & buphthalmos à severe visual impairment Cerebro - Marked hypotonia & hyporeflexia in infancy. Severe progressive mental retardation, behavioural problems Renal – Fanconi’s syndrome (type II(prox) RTA), rickets, osteopenia, path # due to PO4 depletion Diagnosis – detection of phosphatidyl inositol-4,5-bisphosphate phosphatase enzyme in skin fibroblasts. DNA for gene mutation Prenatal diagnosis is possible Treatment = supportive + OT/ surgery as required Alport Syndrome (prev known as hereditary nephritis) Usually X linked (therefore more in males), can be AR on Chr 2 Genetic defect à incorrect basement membrane protein Blood & protein in urine à scarring & thickening à renal failure Triad of • Glomerulonephritis • End stage renal failure • Sensorineural hearing loss (gradual onset, bilateral) Presentation – usually in 2nd decade Progression – dialysis & transplant in 3rd decade Aarskog Syndrome X linked recessive Features Mild-moderate learning difficulties Short stature Facial dysmorphism – hypertelorism, anteverted nostrils, web neck Shawl scrotum (wraps around penis) Cryptorchidism Barters Syndrome Rare, renal K wasting Salt losing nephropathy with mutations in thick ascending limb of loop on Henle Can be AR inheritance Features Low K+, low Na, Low Cl Metabolic alkalosis WITHOUT vomiting Normal BP, high renin & aldosterone Urine Cl > 20 Pathophysiology Hyperplasia of juxtaglomerular apparatus Primary defect in Cl- re-absorption in ascending limb à excess NaCl in distal tubule à Na absorption & K loss Secondary defect = stimulation of RAA system à worsens K loss Neonatal Barters Polyhydramios (Large urine volume) & prem with growth retardation High weight loss after birth due to high urine production Triangular face with prominent forehead, large eyes, protruding ears, drooping mouth NORMAL BP Raised renin & aldosterone Present in 1st few days of life Classical Barters Polyuria, polydipsia, vomiting, constipation, salt craving, FTT Later fatigue à carpo-pedal spasms NORMAL BP HIGH urine Cl (NB: low urine Cl in diuretics, liquorice, laxatives, D&V, pyelonephritis or DI) Rx – oral K supplements & indomethacin Pseudo-bartter’s syndrome E.g. in CF - Sweating, vomiting, renal salt wasting Also seen in Chloride losing diarrhoea, laxative abuse and diuretic abuse NORMAL Mg & LOW urine Cl Hypophosphataemia Causes Decreased intake e.g. prem, starvation, malabsorption Fluid / Electrolyte shifts e.g. respiratory / metabolic alkalosis, DKA, steroid Increased loss – 1o and 3o hyperparathyroidism, renal tubule defects, diuretics, IVI Combined – vitamin D deficient /resistant rickets Symptoms Muscle weakness à respiratory failure Peripheral neuropathy, coma, seizures Rhabdomyolysis, haemolysis, impaired platelet function Hyperuricaemia Increased cell number / destruction e.g. chemotherapy Decreased renal clearance e.g. aspirin / Downs Increased ketones e.g. DKA. Therefore hyperhydrate prior to chemo Cystinosis AR – Lysosomal storage disease à Accumulation of intracellular cysteine Typically blond hair & blue eyes Defect in membrane transport for cysteine, lysine, ornithine & arginine in proximal tubular cells Features Recurrent nephrolithiasis (accumulation in collecting system) à Renal failure (fanconi) by age 10 Deposits in thyroid & lens à hypothyroid & photophobia DM & muscle wasting Rx - Tranplant is curative Cyclosporin (post renal transplant) Most common side effect is nephrotoxicity (differential = graft rejection) Also hepatotoxic Can cause hypertrichosis (excess hair) & paraesthesia Renal Vein Thrombosis Causes – Infants Sepsis Shock Dehydration Causes – older children Nephrotic syndrome CCF Sx Pain, haematuria, enlarged kidneys Side effects of thiazides Increased cholesterol Low Cl, low K, Low Na, Low Mg, Alkalosis High Ca, High BM, High Urea Low BP GI upset Reversible impotence Rashes & photosensitivity Exacerbation of SLE Non Gonococcal urethritis Mostly due to chlamydia (also mycoplasma, ureaplasma, trichomonas or meningococcus) Also occurs in Reiters Syndrome (urethritis, conjunctivitis, arthritis) Complications – salpingitis, perihepatitis, conjunctivitis & sterility Rx – doxycycline / erythromycin NOT assoc with cystitis or septic arthritis Scrotal Pain Physciological – idiopathic scrotal oedema Pathological Trauma Torsion / hernia / torsion of appendix testis Infection – epididyomo-orchitis HSP