NEPHROLOGY AND UROLOGY

DR SAMED ALSALMI

Anomalies detectable on antenatal ultrasound screening

Absence of both kidneys (renal agenesis) Multicystic dysplastic kidney autosomal recessive polycystic kidney disease pelvic kidney or a horseshoe kidney bladder extrophy Obstruction to urine flow may occur at the pelviureteric or vesicoureteric junction, at the bladder neck (e.g. due to disruption of the nerve supply, neuropathic bladder) or at the posterior urethra in a boy due to mucosal folds or a membrane, known as aposterior urethral valve

Antenatal treatmentThe male fetus with a posterior urethral valve may develop severe urinary outflow obstruction resulting in progressive bilateral hydronephrosis, poor renal growth and declining liquor volume with the potential to induce pulmonary hypoplasia. Intrauterine bladder drainage procedures to prevent severe renal damage have been attempted but results have been disappointing. Early delivery is rarely indicated

Postnatal managementAn example of a protocol for infants with antenatally diagnosed anomalies is shown in . Prophylactic antibiotics should be started at birth to try to prevent urinary tract infection. As the newborn kidney has a low GFR, urine flow is low and mild outflow obstruction may not be evident in the first few days of life. The scan should therefore be repeated several weeks later. Bilateral hydronephrosis in a male infant warrants urgent further investigation to exclude a posterior urethral valve, which always requires surgery

ANTINATAL Dx OF URINARY TRACT ANOMALYPROPHYLACTIC ABBILAT HYDRONEPHROSIS AND OR DILATED LOWER UT AREA IN MALE

UNILAAT DEFECT IN MALE ANY DEFECT IN FEMAL

US WITHIN 48 HRSNORMAL

US WITHIN 6 WKS

ABNORMAL ABNORMAL

MCUG SURGRY

STOP AB REPEATE US WITHIN 3_4 MO FURTHER INVESTIGATION

Assessment of the kidneys and urinary tract

The glomerular filtration rate (GFR) is low in the newborn infant. It is especially low if premature; the GFR at 28 weeks' gestation is only 10% of the term infant, or 30% if corrected for body surface area. In term infants, the corrected GFR doubles in the first two weeks after birth, increasing fourfold from birth to 1-2 years of age when the adult rate of 120ml/min per 1.73m 2 is achieved. The assessment of renal function in children is listed in and the radiological investigations of the kidneys and urinary tract

Assessment of renal function in children

Plasma creatinine concentration

Rises progressively throughout childhood according to height and muscle bulk. Plasma creatinine may not rise above normal for age until renal function has fallen to less than half normal.

Glomerular filtration rate (GFR)

A rough estimate of GFR can be obtained using the formula: HT (CM)*40 divided by plasma creatinine mcmol

measuring the clearance More accurate measurement of GFR is by measuring the clearance from the plasma of a substance that is freely filtered at the glomerulus and is not secreted or reabsorbed by the tubules (e.g. creatinine inulin, EDTA). The need for repeated blood tests limits its use in children.:The renal clearance of a substance x (C ) is calculated asx

Cx=UxV/Pxwhere V is the urine flow rate (ml/min) and U and P are the urine and plasma concentrations of substance x, respectively C is expressed as ml/min, and is usually idealized adult body surface area normalized to a standard 1.73m (i.e. Cx is inx x x 2

ml/min/1.73m2) by the factor 1.73/BSA, where BSA is the body surface area (in m2) of the examined subjec

Creatinine clearance

Rarely measured in children because of the difficulties in collecting a complete, timed urine sample.

Determination of GFR by radionuclide scanEstimation of GFR by use of radioisotopes is a commonly used echnique in children, particularly with the limited availability of inulin and difficulties in collecting accurate timed urines in children

Urine analysisdipsticksAppearance Fresh urine generally ranges from pale yellow to deep amber

Odor The normal odor of urine is mildly aromaticpH Urine pH normally ranges from 4.5 to 8 Specific gravity and osmolality Urine osmolality is the key indicator of urinary concentration, and is maximal after an overnight thirst > 870 mOsm/kg inchildren > 2 years Protein Blood HB Glucose

Nitrite More than 90% of common urinary pathogens are nitrite forming

bacteria

Microscopic analysis of urineRed blood cells In healthy children, the normal upper limit for the number of RBCs in fresh midstream urine is 105 colony-forming units of a single organism per millilitre in a properly collected specimen gives a 90% probability of infection. If the same result is found in a second sample, the probability rises to 95%. A growth of mixed organisms usually represents contamination, but if there is doubt, another sample should be collected. Any bacterial growth of a single organism per millilitre in a suprapubic aspirate or catheter sample is considered diagnostic of infection

Test urine sample in infants and children with symptoms and signs of UTI

with unexplained fever of 38C or higher (test urine after 24 hours at the latest). with an alternative site of infection but who remain unwell (consider urine test after 24 hours at the latest

Contributing factors in some children are: infrequent voiding vulvitis hurried micturition constipation neuropathic bladder vesicoureteric reflux.

The following risk factors for UTI and serious underlying pathology should be recorded: poor urine flow history suggesting previous UTI or confirmed previous UTI recurrent fever of uncertain origin antenatally-diagnosed renal abnormality family history of vesicoureteric reflux (VUR) or renal disease constipation dysfunctional voiding enlarged bladder abdominal mass evidence of spinal lesion poor growth high blood pressure.

Indications for culture:diagnosis of acute pyelonephritis/upper urinary tract infectionhigh to intermediate risk of serious illness under 3 years

a single positive result for leukocyte esterase or nitriterecurrent UTI

infection that does not respond to treatment within 2448 hclinical symptoms and dipstick tests do not correlate

ManagementPrompt treatment reduces the risk of renal scarring. Most children can be treated with oral antibiotics (e.g. co-amoxiclav for 5 days, or for 10 days if the child was systemically unwell), adjusting the choice of antibiotic according to sensitivity on urine culture. All infants, and all children who are severely ill, require intravenous antibiotic therapy e.g. cefotaxime or cefuxim and an aminoglycoside such as gentamicin, monitoring its serum levels) until the temperature has settled, when oral treatment is substituted

Follow-up of children with recurrent UTIs, renal scarring or reflux

Urine culture should be checked with a non-specific illness in case it is caused by a UTI (urine should not be cultured routinely). Long-term low-dose antibiotic prophylaxis can be used. There is no evidence for when antibiotic prophylaxis should be stopped. Consideration should be at the age of 2 years (by when maximum renal growth has occurred) or after 1 year free of UTIs. Circumcision in boys may be considered as there is evidence that it reduces the incidence of urinary tract infection. Anti-reflux surgery may be indicated if there is progression of scarring with ongoing reflux, but it has not been shown to improve outcome. Blood pressure should be checked annually if renal defects are present. Regular assessment of growth and renal function is necessary if there are bilateral defects because of the risk of chronic renal failure If there are further symptomatic UTIs in younger children, investigations are required to determine whether there are new scars or continuing reflux. New scars are rare in previously unscarred kidneys after 4 years of age, even in the presence of continuing VUR, and reinvestigation is rarely indicated after this age.

Follow-up No follow-upInfants and children who do not undergo imaging investigations should not routinely be followed up. When results are normal, a follow-up outpatient appointment is not routinely required. Inform parents or carers of the results of all the investigations in writing. Infants and children who are asymptomatic following an episode of UTI should not routinely have their urine re-tested for infection Asymptomatic bacteriuria is not an indication for follow-up

Referral and assessmentInfants and children who have recurrent UTI or abnormal imaging results should be assessed by a paediatric specialist Assessment of infants and children with renal parenchymal defects should include height, weight, blood pressure and routine testing for proteinuria Infants and children with a minor, unilateral renal parenchymal defect do not need longterm follow-up unless they have recurrent UTI or family history or lifestyle risk factors for hypertension.

Long-term follow-upInfants and children who have bilateral renal abnormalities, impaired kidney function, raised blood pressure and/or proteinuria should receive monitoring and appropriate management by a paediatric nephrologist to slow the progression of chronic kidney disease

protocol for management of UTIPROVEN 1ST UTIMEDICAL PREVENTIVE MEASURMENT

START AB US ABNORMAL KIDENY AND URETER

PELVIC DILATION ONLY UROLOGICAL OPINION

NORMAL BLADDER ABNORMAL KIDNEY AND URETER

NORMAL

MALE

FEMAL

RISKY PT IF > 3YRS MGA AND IRS MCUG AND DMSA IF 0.2mg/dL:mg/dL) of on an early morning urine specimen Quantitative Normal: 1000 mg/m2/day in a timed 12- to 24-ho

Workup of a Child with Proteinuria Pediatricians Workup: Phase I Early morning urinalysis to include examination of the sediment Ambulatory and recumbent urinalyses for dipstick protein testing Pediatricians Workup: Phase II Blood electrolytes, BUN, creatinine, serum proteins, Cholesterol ASO titer, C3 complement, ANA Timed 12-hour urine collections, recumbent and ambulatory Renal ultrasonography, IVP, voiding cystourethrography Pediatric Nephrologists Workup: Phase III Renal biopsy

When to Consider Renal Biopsy in a Child with Proteinuria

Strong family history of chronic nephritis or unexplainedrenal failure Unexplained failure to thrive Coexistent hypertension and nephrotic syndrome, or evidence of a systemic inflammatory process Coexistent significant hematuria (>10 erythrocytes/hpf) with Nephrotic-range proteinuria with poor response to prednisone Renal glomerular insufficiency Biochemical evidence of renal tubular dysfunction(e.g., renal tubular acidosis, Fanconi syndrome

When to Refer the Child with Proteinuria to a NephrologistPersistent nonorthostatic proteinuria A family history of glomerulonephritis, chronic renal failure, or kidney transplantation Systemic complaints such as fever, arthritis or arthralgias, and rash Hypertension, edema, cutaneous vasculitis, or purpura

Coexistent hematuria with or without cellular castsElevated blood urea nitrogen (BUN) and creatinine levels or unexplained electrolyte abnormalities

Nephrotic syndrome

In nephrotic syndrome, heavy proteinuria results in a low plasma albumin and oedema. The cause of the condition is unknown, but a few cases are secondary to systemic diseases such as Henoch-Schnlein purpura (HSP) and other vasculitides, e.g. systemic lupus erythematosus (SLE), infections e.g. malaria or allergens e.g. bee sting).

diagnosis of nephrotic syndromerequires the presence of edema, severe proteinuria (> 60 mg/m2/h, or a protein:creatinine ratio > 2.0), hypoalbuminemia (< 2.5 g/dl), and hyperlipidemia.>4,5 Steroid-sensitive nephrotic syndrome Patients who enter remission in response to corticosteroid treatment alone are referred to as having steroid-responsive or steroid-sensitive nephrotic syndrome FROM 2 TO 10 YRS M>F WITH MILD INTERMITTENT H UREA WITH NORMAL BP AND RENAL FUNCTION Remission of nephrotic syndrome Remission represents a marked reduction in proteinuria to < 4 mg/m2/h, or urine albumin dipstick of 0 to trace for 3consecutive days in association with resolution of edema .Relapse of nephrotic syndrome Relapse of nephrotic syndrome is defined as recurrence of severe proteinuria (> 60 mg/m2/24h, +++ of dipestic on 3 successive days often with a recurrence of edema

.

Steroid-resistant nephrotic syndromestate as a failure to develop remission after 4 weeks of prednisone at a dose of 60 mg/m2/day MORE THAN 10 AND LESS THAN 2YR WITH PERSISTANT H UREA HIGH BP AND RENAL DYSFUNCTION

Steroid-dependent nephrotic syndromeSome patients respond to initial steroid treatment by developing complete remission, but develop a relapse either while still receiving steroids, or within 2 weeks of discontinuation of treatment following a steroid taper. Such patients typically may require continued low-dose treatment with steroids to prevent this rapid development of relapse, and are therefore referred to as having steroid-dependent nephrotic syndrome

Frequently relapsing nephrotic syndromeIf patients develop 4 or more episodes of nephrotic syndrome in any 12-month period, they are referred to as having frequently relapsing nephrotic syndrome FRNS

causes of nephrotic syndrome in childrenPrimary causesMinimal change nephrotic syndrome MCNS Focal segmental glomerulosclerosis FSGS Membranoproliferative glomerulonephritis MPGN mesangiocapillary glomerulonephritis MPGN type I MPGN type II dense deposit disease MPGN type III

Membranous nephropathy MN

Secondary causesSystemic diseases associated with nephrotic syndrome HenochSchnlein purpuraSystemic lupus erythematosus Diabetes mellitusSarcoidosis Infectious diseases associated with NS: Hepatitis B usually associated with MN Hepatitis C usually associated with MPGN HIV often with FSGS Hematology/oncology: LeukemiaLymphoma Hodgkin disease usually MCNS Sickle cell anemia Drugs: NSAIDS MCNSGold Penicillamine Captopril

Steroid-resistant nephrotic syndromeCause Specific features Prognosis

Focal segmental glomerulosclerosis

Most common Familial or idiopathic With HIV NORMAL C3 C4 Rx alternative steroid enalopril

30% progress to end-stage renal failure in 5 years; 20% respond IN 20% to cyclophosphamidel ", vincristine or ciclosporin. Recurrence post transplant is common 30% Decline in renal function over many years

Mesangiocapillary glomerulonephritis (membranoproliferative glomerulonephritis) Membranous nephropathy

More common in older children with HCV Haematuria and low C3 C4 level present Associated with HBV May precede SLE GOLD PENCILINAMIN

Most remit spontaneously within 5 years

Steroid-sensitive nephrotic syndrome

In 85-90% of children with nephrotic syndrome, the proteinuria resolves with corticosteroid therapy (steroidsensitive nephrotic syndrome). These children do not progress to renal failure. It is commoner in boys than in girls, in Asian children than in Caucasians and there is a weak association with atopy. It is often precipitated by respiratory infections. Features suggesting steroidsensitive nephrotic syndrome are: age between 1 and 10 years no macroscopic haematuria normal blood pressure normal complement levels normal renal function

Clinical signs of the nephrotic syndrome are : periorbital oedema (particularly on waking), the earliest sign scrotal or vulval, leg and ankle oedema ascites breathlessness due to pleural effusions and abdominal distension.

Investigations performed at presentation of nephrotic syndromeUrine protein - on test strips ('Dipstick') Full blood count and ESR Urea, electrolytes, creatinine, albumin Complement levels - C3, C4 Antistreptolysin O titre and throat swab Urine microscopy and culture Urinary sodium concentration

Hepatitis B antigen

Consideration of renal biopsy

those older than 10 years undergoing a biopsy because of the higher likelihood of finding a histologic lesion other than MCNS

Children who do not respond to 4-8 weeks of corticosteroid therapy or have atypical features may have a more sinister diagnosis and require a renal biopsyRenal histology in steroid-sensitive nephrotic syndrome is usually normal on light microscopy but fusion of the specialised epithelial cells that invest the glomerular capillaries (podocytes) is seen on electron microscopy. For this reason it is called minimal change disease. .

Congenital nephrotic syndromepresents in the first 3 months of life. It is rare. The commonest kind is recessively inherited and the gene frequency is particularly high in Finns. It is associated with a high mortality, usually due to complications of hypoalbuminaemia rather than renal failure. The albuminuria is so severe that bilateral nephrectomy may be necessary for its control, inevitably precipitating the need for dialysis, which is then continued until the child is large and fit enough for renal transplantation about 10 KG.

Complication

HypovolaemiaDuring the initial phase of oedema formation the intravascular compartment may become volume depleted. The child who becomes hypovolaemic characteristically complains of abdominal pain and may feel faint. There is peripheral vasoconstriction and urinary sodium retention. A low urinary sodium (2 /6mo (steroid dependence)Relapses are identified by parents on urine testing. The side-effects of corticosteroid therapy may be reduced by an alternate-day regimen. Treatment of infrequent relapse with prednislon 60mg perM2 per day until remession then 40 then 30 then 20 then 10 then 5mg per M2 per day 3 days for every one on alternative day aboute 15 doses If relapses are frequent or if a high maintenance dose is required ( dependence), involvement of a paediatric nephrologist is advisable as other drug therapy may be considered. Levamisole, an immunomodulator, may maintain remission. An 8-week course of alkylating agents maintains remission in 25-30% of steroid-dependent children for 2 years. Ciclosporin A maintains remission in about 75% of patients while it is being taken, but relapse almost always occurs when it is stopped.Steroid-resistant nephrotic syndrome treatment These children should be referred to a paediatric nephrologist. Management of the oedema is by diuretic therapy, salt restriction, ACE inhibitors and sometimes NSAIDs (non-steroidal anti-inflammatory drugs), which may reduce proteinuria.

HematuriaUrine which is red in colour or tests positive for haemoglobin on urine sticks should be examined under the microscope to confirm haematuria (>10 red blood cells per high-power field).

Glomerular haematuriais suggested by brown urine, the presence of deformed red cells (which occurs as they pass through the basement membrane) and casts, and is often accompanied by proteinuria .

Lower urinary tract haematuriais usually red, occurs at the beginning or end of the urinary stream, is not accompanied by proteinuria and is unusual in children. Urinary tract infection is the most common cause of haematuria although seldom as the only symptom. The history and examination may suggest the diagnosis, e.g. a family history of stone formation or nephritis or a history of trauma.

Causes of red or dark-colored urineMacroscopic hematuria Myoglobinuria Hemoglobinuria Biologic pigments:Bilirubin Urates Inborn errors of metabolism: Alkaptonuria Tyrosinosis Porphyrinuria

Drugs and food colors: ChloroquineDesferrioxamineDiphenylhydantoin MetronidazoleNitrofurantoinPhenolphthalein RifampinSulfa drugsFood/dyesBeets

Causes of haematuriaNon-glomerular Infection (bacterial, viral, TB, schistosomiasis) Trauma to genitalia, urinary tract or kidneys Stones Tumours Sickle cell disease Bleeding disorders Renal vein thrombosis Hypercalciuria Glomerular Acute glomerulonephritis (usually with proteinuria) Chronic glomerulonephritis (usually with proteinuria) IgA nephropathy Familial nephritis Thin basement membrane disease

causes of hemoglobinuria and myoglobinuriaHemoglobinuriaHemolytic anemia(G6PD) Mismatched blood transfusions Sepsis/disseminated intravascular coagulation DIC Freshwater near drowning Toxins

MyoglobinuriaRhabdomyolysis Myositis Severe muscle injury

Important aspects of history and physical examination in evaluation of hematuriaPatient historyExercise Menstruation Trauma Medication Recent URI/impetigo Dysuria/frequency/urgency Suprapubic/abdominal/costovertebral angle pain Myalgias/arthralgias Stone passage Timing of hematuria throughout/initiation/termination of urine stream

Family historyChronic kidney disease Hematuria Deafness Hypertension Nephrolithiasis Hemoglobinopathy Coagulopathy

Physical examinationHypertension Fever Edema Rash Arthritis Costovertebral angle tenderness Abdominal mass URI,

Investigation of haematuria

All patients Urine microscopy (with phase contrast) and culture Protein and calcium excretion Kidney and urinary tract ultrasound Plasma urea, electrolytes, creatinine, calcium, phosphate, albumin Full blood count, platelets, clotting screen, sickle cell screen

If suggestive of glomerular haematuria ESR, complement levels and anti-DNA binding Throat swab and antistreptolysin O titre Hepatitis B antigen Renal biopsy if indicated Test mother's urine for blood (if Alport's syndrome suspected) Hearing test (if Alport's syndrome suspected

Acute nephritisCauses of acute nephritis Post-infectious including streptococcus Vasculitis (Henoch-Schnlein purpura or, rarely, SLE, Wegener's granulomatosis, microscopic polyarteritis, polyarteritis nodosa) IgA nephropathy and mesangiocapillary glomerulonephritis Anti-glomerular basement membrane disease (Goodpasture's syndrome) - very rare Acute nephritis in childhood usually follows a streptococcal sore throat or skin infection. Streptococcal nephritis is a common condition in the developing world, but has become uncommon in the UK.. In acute nephritis, increased glomerular cellularity restricts glomerular blood flow and therefore filtration is decreased. This leads to: decreased urine output and volume overload hypertension, which may cause seizures oedema, characteristically around the eyes haematuria and proteinuria.

Conditions that present as acute nephritic syndrome. Acute postinfectious glomerulonephritisBacterial infections: Poststreptococcal glomerulonephritisStaphylococciPneumococciYersinia Mycoplasma pneumoniae

Viral infections:Influenza virusAdenovirusCoxsackie virusCytomegalovirus EpsteinBarr virusVaricella virusMumps virus Measles virusParvovirus B19 . Membranoproliferative glomerulonephritis

. IgA nephropathy HenochSchnlein purpura nephritis Systemic lupus erythematosus nephritis Rapidly progressive glomerulonephritis

VasculitisMicroscopic polyangitisWegeners granulomatosis ChurgStrauss syndrome

GlomerulonephritisRefers to that variety of kidney disease in which proliferation and inflammation of the glomerulus is secondary to an immunologic mechanism. Presentation of GN varies from microscopic asymptomatic hematuria proteinuria acute nephritis, rapidly progressive nephritis.

Nephritic Syndrome

Hematuria dysmorphic red blood cells, red blood cell casts Azotemia Oliguria Hypertension Variable proteinuria Nephrotic syn 10%

Focal Proliferative Glomerulonephritis

IgA nephropathy Henoch-Schonlein purpura Lupus nephritis class II and III

Heriditary nephritis Alports syn

Diffuse Proliferative Glomerulonephritis

Poststreptococcal glomerulonephritis Bacterial endocarditis Lupus nephritis (Class IV)

Membranoproliferative glomerulonephritis Crescentic glomerulonephritis Vasculitis

Post-streptococcal nephritisThis is diagnosed by evidence of a recent streptococcal infection (culture of the organism, raised ASO titre) and low complement C3and CH50 levels that return to normal after 3-4 weeks DIFFUSEDD PROLIFRATIVE. Long-term prognosis is good

Clinical presentation The onset of APSGN typically occurs 714 days after an upper respiratory tract infection, and as long as 6 weeks after impetigo.

ManagementAcute postinfectious glomerulonephritisThe treatment of AGN consists of supportive therapy only. Children without volume expansion, hypertension, electrolyte problems, or decreased kidney function need only close followup Patients who develop significant renal impairment or hyperkalemia generally require hospitalization for monitoring and appropriate fluid and electrolyte management Antibiotics Antibiotic treatment after the onset of APSGN does not alter the course of the disease. Antibiotic prophylaxis given to family members may reduce the risk of spread of APSGN. Fluid overload and hypertension When present, hypertension is the result of sodium retention and volume expansion. Therefore, treatment is directed at sodium restriction and diuretic therapy, in addition to antihypertensive medication, if necessary. The combination of aloop or thiazide diuretic with a calcium channel blocker is usually effective. Caution should be exercised with the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers because of the risk of hyperkalemia or renal failure Hyperkalemia Potassium intake should be restricted. If serum potassium is rising, potassium exchange resin, sodium polystyrene sulfonat (Kayexalate), can be administered orally. Life-threatening hyperkalemia should be treated as an emergency using intravenous bicarbonate, glucose, and insulin, or calcium gluconate as appropriate. Rare cases of severe or symptomatic hyperkalemia should be treated with dialysis Dialysis Hemodialysis or continuous venovenous hemofiltration may be necessary in severe cases with uremia, especially if diuretic unresponsive anuria or oliguria is present

Henoch-Schnlein purpurais the combination of: characteristic skin rash arthralgia periarticular oedema abdominal pain glomerulonephritis. It usually occurs between the ages of 3 and 10 years, is twice as common in boys, peaks during the winter months and is often preceded by an upper respiratory infection.. It is postulated that genetic predisposition and antigen exposure increase circulating IgA levels and disrupt IgG synthesis. The IgA and IgG interact to produce complexes that activate complement and are deposited in affected organs, precipitating an inflammatory response with vasculitis.

Clinical findingsAt presentation, affected children often have a fever. The rash is the most obvious feature. It is symmetrically distributed over the buttocks, the extensor surfaces of the arms and legs, and the ankles. . The rash may initially be urticarial, rapidly becoming maculopapular and purpuric, is characteristically palpable and may recur over several weeks.

The rash is the first clinical feature in about 50% and is the cornerstone of the diagnosis, which is clinical.Joint pain occurs in two-thirds of patients, particularly of the knees and ankles. There is periarticular oedema. Long-term damage to the joints does not occur, and symptoms usually resolve before the rash goes. Colicky abdominal pain occurs in many children and, if severe, can be treated with corticosteroids. Gastrointestinal petechiae can cause haematemesis and melaena. Intussusception can occur and can be particularly difficult to diagnose under these circumstances. Ileus, protein-losing enteropathy, orchitis and occasionally central nervous system involvement are rare complications.

Renal involvement is common, but is rarely the first symptom. Over 80% have microscopic or macroscopic haematuria or mild proteinuria with normal complement. These children usually make a complete recovery. If proteinuria is more severe, nephrotic syndrome may result. Risk factors for progressive renal disease are heavy proteinuria, oedema, hypertension and deteriorating renal function, when a renal biopsy will determine if treatment is necessary. All children with renal involvement are followed for a year to detect those with persisting urinary abnormalities (5-10%) who require long term follow-up. This is necessary as hypertension and declining renal function may develop after an interval of several yearsRx may need steroid azithoprime and cyclophosphamide

IgA Nephropathy BERGER DISEASE

Recurent gross H. urea Males > Females Normal complement

This may present with episodes of macroscopic haematuria, commonly in association with upper respiratory tract infections. Histological findings and management are as for Henoch-Schnlein purpura, which may be a variant of the same pathological process but not restricted to the kidney. The prognosis in children is better than that in adults

Rx with ACEI and fish oil may need steroid azithoprim and cyclophosphamid.10% ESRF

Rapidly Progressive Glomerulonephritis

Clinical syndrome

Glomerulonephritis (nephritic syndrome) Rapid decline in renal function Rare 2-4% of all glomerulonephritis Pathologic hallmark crescents Classified based on presence or absence of immune complexes No deposition by electron micrscope

anti-gbm disease ( goodpauster )Clinical presentation

60-70% present with pulmonary hemorrhage Systemic symptoms - malaise, fatigue, anorexia, weight loss, arthralgias, myalgias Caucasians No deposition by electron micrscope

Systemic Lupus Erythematosis

It is characterised by the presence of multiple autoantibodies, including antibodies to double-stranded DNA. The C3 and C4 component of complement may be low, particularly during active phases of the disease. Haematuria and proteinuria are indications for renal biopsy, as immunosuppression is always necessary and its intensity will depend on the severity of renal involvement.

Complex multisystem autoimmune disease Kidney is most common organ involved (50-75%) Females > Males African-Americans and asian have higher rates of lupus nephritis than cucasian

Classification of Lupus Nephritis

Class I Class II Class III Class IV Class V Class VI

normal variable focal mesangial hypercellularity and immune deposits focal proliferative glomerulonephritis diffuse proliferative glomerulonephritis membranous nephropathy chronic glomerulosclerosis

familial nephritis (alport syn)

The commonest familial nephritis is Alport's syndrome. This is usually an X-linked recessive disorder that progresses to end-stage renal failure by early adult life in males and is associated with nerve deafness and ocular defects. The mother may have haematuria.

Vasculitisrenal involvement may occur in rarer vasculitides such as

polyarteritis nodosa, microscopic polyarteritis Wegener's granulomatosis.Characteristic symptoms are fever, malaise, weight loss, skin rash and arthropathy with prominent involvement of the respiratory tract in Wegener's disease. ANCA (antineutrophil cytoplasm antibodies) are present and diagnostic in these diseases. Renal arteriography, to demonstrate the presence of aneurysms, will diagnose polyarteritis nodosa. Renal involvement may be severe and rapidly progressive. Treatment is with steroids, plasma exchange and intravenous cyclophosphamide, which may need to be continued for many months.

Classification of the vasculitides by vessel sizeLarge-vessel vasculitis:Giant cell (temporal) arteritis Takayasus arteritis

Medium-vessel vasculitis:Polyarteritis nodosa Kawasaki disease

Small-vessel vasculitis (pauci-immune-mediated):Wegeners granulomatosis ChurgStrauss syndrome

Small-vessel vasculitis (immune-mediated associated):HenochSchnlein purpura Systemic lupus erythematosus Rheumatoid vasculitis Anti-glomerular basement membrane disease Serum sickness vasculitis Behet disease Scleroderma-associated vasculitis Dermatomyositis-associated vasculitis

Evaluation of acute nephritic syndromeInitial evaluationBlood count (rule out HUS) BUN, creatinine, electrolytes, serum albumin Quantify proteinuria (urine protein:creatinine ratio) Culture of throat and skin lesions Streptococcal antibody titers (ASO, anti DNase B, antihyaluronidase) Complement C3, C4

Further evaluation(If the diagnosis of APSGN is ruled out) Monitor BUN, creatinine, electrolytes Hepatitis B panel, hepatitis C titer ANA (full lupus panel if ANA positive) ANCA Anti-GBM antibody titer (if pulmonary involvement) Renal biopsy

Low

serum complement level

Systemic diseases

SLE low C3 and C4Subacute bacterial endocarditis low C3 Cryoglobulinemia

Renal diseases

Acute poststreptococcal glomerulonephritis (90%)low C3 Membranoproliferative glomerulonephritis (90%)low C3 and C4

Managementis by attention to both water and electrolyte balance and the use of diuretics when necessary. Rarely, there may be a rapid deterioration in renal function (rapidly progressive glomerulonephritis). This may occur with any cause of acute nephritis, but is uncommon when the cause is post-streptococcal. If left untreated, irreversible renal failure may occur over weeks or months, so renal biopsy and treatment with immunosuppression and plasma exchange should be undertaken promptly

Renal massesCauses of palpable kidneys Unilateral Multicystic kidney Compensatory hypertrophy Obstructed hydronephrosis Renal tumour (Wilms' tumour) Renal vein thrombosis Bilateral Autosomal recessive (infantile) polycystic kidneys Autosomal dominant (adult) polycystic kidneys Tuberous sclerosis Renal vein thrombosisAn abdominal mass identified on palpating the abdomen should be investigated promptly by ultrasound scan. Bilaterally enlarged kidneys in early life are most frequently due to autosomal recessive polycystic kidney disease, which is associated with hypertension, hepatic fibrosis and progression to chronic renal failure. This form of polycystic kidney disease must be distinguished from the autosomal dominant adult-type polycystic kidney disease, which has a more benign prognosis.

Renal calculiRenal stones are uncommon in childhood . When they occur, predisposing causes must be sought: urinary tract infection structural anomalies of the urinary tract metabolic abnormalities. The commonest are phosphate stones associated with infection, especially with Proteus. Calcium-containing stones occur in idiopathic hypercalciuria, the most common metabolic abnormality, and with increased urinary urate and oxalate excretion. Deposition of calcium in the parenchyma (nephrocalcinosis) may occur with hypercalciuria, hyperoxaluria and distal renal tubular acidosis. Nephrocalcinosis may be a complication of furosemide therapy in the neonate. Cystine and xanthine stones are rare. Presentation may be with haematuria, loin or abdominal pain, UTI or passage of a stone. Stones that are not passed spontaneously should be removed, by either lithotripsy or surgery, and any predisposing structural anomaly repaired. A high fluid intake is recommended in all affected children. If the cause is a metabolic abnormality, specific therapy may be possible

Acid-Base and Electrolyte Disturbances

Normal ABG PH: 7.35-7.45 pO2 : 11-14 (80 -100) pCO2 : 4.5-6 (35 - 45) HCO3: 22 - 26 BD/BE: (25 - HCO3)

Clinical tools for evaluation for acid base balanceAnion gap .Na (HCO3

+ Cl ) =AG

An AG between 8 and 16 is normal;

Osmolar gap = Measured Osmolality Calculated Osmolality Normal = 16)

URINE HCO3 LOSS

PERSISTENT DIARRHEA

RTA

RTA

SERUM K

HIGH

LOW

ALDESTERON

URINE PH

HIGH

LOW

LESS THAN 5.5

MORE THAN 5.5

ALDESTERON RESISTANCE RTA IV

ALDESTERO N DEFICIENCY RTA IV

Renal tubular acidosis II(

FANCONI(

RTA I DISTAL +NEPHROCACINOSIS + DEAFNRSS

INBORN ERRORS OF METABOLISM ASSOCIATED WITH RENAL TUBULAR DYSFUNCTION AND M ACIDOSIS WITH NORMAL A GAP

Lysosomal disorder ( (Lowe sy) (wilson) (cystinosis) amino acid disorder (Hepatorenal tyrosinemia( charabohydrate disorder hereditary fructose intolerance galactosemia Glycogen storage disease, type I

Renal tubular acidosis II(

FANCONI(

Lysosomal disorder Lipid storage disorders (sphingolipidoses) and mucopolysaccharidoses Present in subacute way, after a period of normal development, with regression organomegaly with enlargement of the liver and/or spleen coarse facies, with or without accompanying biochemical upset such as hypoglycaemia

Disorders

of carbohydrate metabolism There are sever hypoglycemiaM

Amino

acid disorders There are hypoglecemia M acidosis with normal AG High ketonNormal

acidosis with normal A.G Normal ammonia High ketonhigh

lactate < 2mmol

lactate

Hyperammonia >50mmol

LOW PH HCO3 AND PCO2 METABOLIC ACIDOSIS

HIGH PLASMA ANION GAP

LACTIC ACID

NORMAL

HIGH

HYPOPERFUSION OSMOLAR GAP HIGH >10 NORMAL 20mmol/L: Bartter Syndrome & Gitelman syndrome Low < 10mmol/L: Pseudo-Bartter disorders Except Lasix use 1. Skin: Cystic fibrosis or excessive sweating 2. GIT: Upper Pyloric stenosis, excessive vomiting or NGT suction Lower Chloride diarrhea or laxative abuse 3. Renal: Loop diuretic Furosemide use D. Hypertensive M. Alkalosis: Check Renin & Aldosterone Both High: Renal artery stenosis Both Low: Liddles disease, CAH 11 or Coushing disease Renin&Aldosterone: Hyperaldosteronism Conns disease or Tumor Liddles disease is due to overactive overexpression of Aldosterone receptors on the distal tubules, so it acts as hyperaldosteronism is spite of low Aldosterone Psudo E. Management: Reverse the cause: treat the cause Fluid replacement: Fluid, Chloride & K+ Saline & KCL for Normal BP Antihypertensive: Not ACEI or ARB for high BP Surgery: For renal artery stenosis or Tumor

Differential Diagnosis of Metabolic Alkalosis Urinary Chloride < 10 mEq/L Low chloride intake vomiting, nasogastric suctioning congenital chloride diarrhea, Diuretic therapy (prolonged) Cystic fibrosis Urinary Chloride > 20 mEq/L With Hypertension High renin, high aldosterone Renal artery stenosis Renin-secreting tumors Low renin, high aldosterone Primary hyperaldosteronism (conn syn) or (tumer) Low renin, low aldosterone 11--Hydroxylase deficiency Liddle syndrome Cushing syn With Normal Blood Pressure Bartter syndrome Gitelman syndrome Diuretic therapy (recent)

SCHEDULE FOR METABOLIC ALKALOSISHIGH PH HCO3 LOWPCO2 METABOLIC ALKALOSIS

SERUME CLLOW BP NORMAL

EXOGEOUSE HCO3 HIGHRENINE AND ALDESTERON LOW RENINE HIGH ALDES

NORMALURINE CL HIGH > 20 BARTTER AND GITELMAN WITH HIGH RENINE AND ALDESTERON NORMAL < 10PSEUDOBARTTER SYN Skin: Cystic fibrosis or excessive sweating 2. GIT: Upper Pyloric stenosis, excessive vomiting or NGT suction Lower Chloride diarrhea or laxative abuse 3. Renal: Loop diuretic Furosemide use

ALL HIGH

ALL LOW

RAS

LIDDLE CAH 11BH CUSHING

CONN. SY ADRE. TUMER

Respiratory Acidosis

{ lowPH, high pCO2, high HCO3 & low pO2} Steps of Thinking: 1. Patient is not ventilated 2. Ventilated patient A. Patient is not ventilated : HYPOVENTILATION Conservative management: Treat the respiratory disorder & monitor Ventilation: consider it if no improvement or deteriorating Initial ventilation setting is individualized out the scope of this synopsis B. Ventilated patient : Raise the ventilation parameters FiO2 = Improve Oxygenation Vent.rate = Improve CO2 Hypoventilation PEEP = improve Oxygenation & Raise CO2 Ti = improve Oxygenation & Raise CO2 PiP = improve both TV = improve both

Renine angiotensin change with renal diseasesrenine hyperrenemia hyporenemia High aldesteron High BP LOW K

Low aldesteron Low BP High BP

N BP

Low BP

High aldes.

Low aldes.

Addisn CAH (17oh)

Sec Hyper Aldesteronism (RAS)

Bartter gietlm an

Psedo Hypo aldeseronism

Conn Adernal tumer

Liddle CAH 11Boh cushing

Disorders of tubular transportProximal tubular disorders Selective transport defects: CystinuriaHartnup disease Fanconi syndrome: CystinosisLowe syndromeTyrosinemiaWilson disease GalactosemiaFructosemiaMitochondrial cytopathies Disorders of distal nephron Salt-wasting defects: Bartter syndromeGitelman syndromePseudohypoaldosteronism Excess salt-retaining defects: Liddle syndromeGordon syndrome Disorders of magnesium reabsorption Familial hypomagnesemia with hypercalciuria (FHH). Hypomagnesemia with severe hypocalcemia (HSH) Disorders of water reabsorption Nephrogenic diabetes insipidus

Proximal renal tubular acidosis (RTAII)(defective bicarbonate reclamation)

Sporadic:Transient (infants) Cyanotic heart disease Renal vascular accident Genetic: Autosomal dominant Autosomal recessive with mental retardation and ocular disease Leighs syndromeMetachromatic leukodystrophy Carbonic anhydrase inhibition: Topiramate (Topamax) Acetazolamide Sulfanilamide Mafenide

Distal renal tubular acidosis (defective acid secretion)(RTAI) Genetic:Autosomal dominant Autosomal recessive

Hereditary diseases with DRTA:Hereditary elliptocytosis Sickle cell disease Familial hypercalciuriaType 1 glycogen storage disease Nephronophthisis

Hypercalciuria with nephrocalcinosis:Primary hyperparathyroidism Hyperthyroidism Wilson diseaseIdiopathic hypercalciuria

Autoimmune disease:SLEPrimary biliary cirrhosisChronic active hepatitis

Drug- and toxin-induced DRTA:Amphotericin NSAIDs nephropathy LithiumFoscarnet

Tubulointerstitial disease:Chronic pyelonephritis Obstructive nephropathyVesicoureteral reflux

Causes of type IV renal tubular acidosis Aldosterone deficiency:Addison diseaseBilateral adrenalectomy Congenital adrenal hyperplasia Diabetic nephropathy AIDS nephropathyGouty nephropathy bblockersACE inhibitorsHeparin Pseudohypoaldosteronism II(gordon syn)

Aldosterone resistance:Autosomal dominant pseudohypoaldosteronism I Autosomal recessive pseudohypoaldosteronism I Sickle cell nephropathyRenal transplant rejection Analgesic nephropathyNephrocalcinosis/nephrolithiasis SpironolactoneFetal alcohol syndrome

Feature Urine pH during acidosis Urine anion gap Urine-to-blood PCO2 Serum potassium Calcium excretion Nephrocalcinosis Associated tubular defects Rickets Daily alkali requirement (mEq/kg/day) Potassium supplementation

(Distal RTAI) >5.5 Positive