Case Report: Idiopathic Steroid-resistant Nephrotic Syndrome : Case Report: Idiopathic Steroid-resistant Nephrotic Syndrome Eoin Ryan & Davide F. Civita 1st Department of Pediatrics and Adolescent Medicine LF UPJS KOSICE Patient details: Patient details Female patient , born 21/6/2002 2° physiological pregnancy Birth weight : 3200g (25-50 cetile s ) Lenght = 52 cm (75-90 centile s ) APGAR Score (8/10) Current Details: Current Details Age : 11 y.o . Height : 127cm (< 3rd centile) Weight : 24.6 Kg (< 3rd centile) BMI 15.25 (10-25 centile) BP – Hypertensive (>95th) Medical History: Medical History Present from Birth: Psychomotor problems Atypical Autism Nasolacrimal Duct Obstruction Perceptual Disturbance of Hearing Hospitalizations: Hospitalizations 2011 – March : Admitted with Oedema ( eyelids and calves ), Dx . Nephrotic synd . Tx . Prednisolone, Diuretics , Albumin ; April : Kidney biopsy – FSGS ( discovered corticoid resistant )!!! May : Repeated attack ; Tx . Cyclosporin A September : Repeated attack ; Tx . Tacrolimus Hospitalizations: Hospitalizations 2012 – April - admitted with nausea and vominting May - presented with oedema July – ‘’ ‘’ Tx . Rituximab Current Diagnosis: Current Diagnosis PRIMARY STEROID RESISTANT NEPHROTIC synd . Bioptically : FSGS CKD (Stage V, ESRD) Renoparenchymal Hypertension Secondary Anaemia Mild Pan- valvular insufficiency Growth Retardation associated S light mental retardation Atypical Autism PowerPoint Presentation: STAGE V STAGE IV STAGE III STAGE II STAGE I Progressive decrease in GFR/Time Staging of CKD: Staging of CKD Extra-investigations: Extra- investigations Cardiology : IVS hypertrophy & pan- valvular insufficiency ; thrombus formation after cannulation of jugular vein ; Dx and subsequently administered Ticlopidin ; Radiology : DEXA – 1.6 SD (December 2012); Haematolog y : EPO study (February 2013); PowerPoint Presentation: Neurology : Excluded epilepsy ENT : Excluded deafness Endocrinology : negative for any pathology of Thyroid and parathyroid gland ; Psychology : No CAN evidence; Current Therapy: Current Therapy Chronic Haemodialysis - 3x week (long term use) is associated with 250 ml diureis ( loss of kidney filtration function ). PREDNISOLONE 5mg ( this is low dosage as Dx is Steroid Resistant ) EBRANTIL – Urapidil ( alpha 1 - blocker ) AGEN – amlodipine ( Dihydropyridine CCB) TRITACE – Ramipril (ACE inhibitor ) PowerPoint Presentation: ATORIS – Atorvastatin VITACALCIN – CaCO3 OSTEO-D – Calcitriol CALTRATE – Calcium + Vit . D VENOFER – IV Iron Succrose MALTOFER – Oral Iron VITOR – Bicarbonate NEPHROTIC SYNDROME: NEPHROTIC SYNDROME Definition : Nephrotic Syndrome is a manifestation of glomerular disease consisting in: protein loss in the urine, low blood protein levels, high cholesterol levels, high triglyceride levels, and swelling . I – Nephrotic Range Proteinuria ( > 40mg/kg/ day ) II – Hypoalbuminemia ( < 25 g/L ) III – Edema IV – Dyslipidemia Which forms of Nephrotic Synd. Exist?: Which forms of Nephrotic Synd . Exist ? A) PRIMARY or IDIOPATHIC NS MINIMAL CHANGE ( most common) FSGS MEMBRANOUS NEPHROPATHY MEMBRANO-PROLIFERATIVE GLOMERULONEPHRITIS B) TYPICAL NS ( caracterized by mutation on crucial proteins ) DIFFUSE MESANGIAL SCLEROSIS ( laminin β 2 chain ) ‘FINNISH TYPE’ CONGENITAL NS ( nephrine ) This case presents with…: This case presents with… FSGS FSGS: FSGS Definition : Focal segmetal glomerulo sclerosis describes scarring process occurring in the in a certain amount of glomeruli (focal segmental). FSGS is an histologic diagnosis that may be idiopathic / primary or secondary (in response to previous glomerular injury, glomerular hypertension, or hypertrophy).  FSGS: FSGS How it looks like…: How it looks like … PowerPoint Presentation: Etiology : Primary : Idiopathic ; Secondary : Glomerulonephritis , an inflammation of the glomeruli. About 7 to 15% of people with glomeruonephritis (inflammation) develop glomerulosclerosis (scarring) Reflux nephropathy (backward flow of the urine up to the kidney). Kidney-harming chemicals or medicines that damage the glomeruli. Clinical features : Nephrotic Syndrome Dx : Byopsy ( most useful ) New research about causative agent for idiopathic FSGS: New research about causative agent for idiopathic FSGS Overexpression of soluble urokinase Plasminogen Activator Receptor ( suPAR ) causes pathology in animal models similar to primary FSGS, and one recent study demonstrated elevated levels of serum suPAR in patients with the disease (3) What are the signs and symptoms?: What are the signs and symptoms ? Early stages of glomerulosclerosis may not cause any symptoms. develop high blood pressure; proteinuria; If very large amounts of protein are lost in the urine : swelling of the ankles and eyelids, rapid weight gain; Late stage : ( kidney failure) : fatigue , a poor appetite, headache, itchy skin, shortness of breath and/or nausea. What is the treatment?: What is the treatment? 1) CORTICOSTEROIDS – PREDNISOLONE Urine is tested for protein frequently during treatment, because having less urinary protein is a sign that the treatment is working. 2) control blood pressure ACE inhibitors & ARBs & DIURETICS (FUROSEMIDE). 3) DIETARY CHANGES – Na, Proteins & Fluid restiction . What does happen, if the CORTICOSTEROIDS don’t work? : What does happen , if the CORTICOSTEROIDS don’t work? We are dealing with: IDIOPATHIC STEROID-RESISTANT NEPHROTIC SYNDROME ETIOLOGY?: ETIOLOGY? SINGLE GENE MUTATIONS 25%- 30% of patients with SRNS in many parts of the world have shown single gene mutations affecting glomerular podocyte differentiation and function . NPHS1 ( encodes nephrin ) NPHS2 ( encodes podocin ) WT1 ( encodes the transcription of tumor suppressor protein , involved in kidney and gonad development ) So what is the treatment?: So what is the treatment? IMMUNOSUPPRESSIVE Tx – Alkylating agents Calcineurin inhibitors ( CNIs ) – Cyclosporine & Tacrolimus Mycophenolate mofetil Rituximab ANGIOTENSIN ANTAGONISM – ACE inhibitors or ARBs ; ( This reduces protein excretion ) But…: But … The progression goes more o less faster towards : ESKD (End Stage Kidney Disease ) is inevitable …. So it is necessary to put the patient in list for a TRANSPLANTATION Recurrence of FSGS in Allograft: Recurrence of FSGS in Allograft The transplantation it is the final solution but due to the recurrence of FSGS, the patient will necessitate in future of an additional transplant procedure of kidneys . Patient is on waiting list for transplant, however FSGS has high risk of recurrence between 20,5 and 50% according to pediatric trials of ‘North American Pediatric renal Transplant Cooperation Study’ and ‘ Uptodate ’ respectively. ( 1 ) The End : The End PowerPoint Presentation: Uptodate: http :// www.uptodate.com/contents/focal-segmental-glomerulosclerosis-in-the-transplanted-kidney 2. Pubmed : http:// www.ncbi.nlm.nih.gov/pubmed/23138488 4. Uptodate: The many masks of focal segmental glomerulosclerosis . Agati . Kidney Int. 1994;46(4):1223. 3. Uptodate: Absence of hypoalbuminemia despite massive proteinuria in focal segmental glomerulosclerosis secondary to hyperfiltration . Praga M, Morales E, Herrero JC, Pérez Campos A, Domínguez -Gil B, Alegre R, Vara J, Martínez MA Am J Kidney Dis. 1999;33(1):52 .