Alport's syndrome and benign familial haematuria: light and electron microscopic studies of the kidney

INTRODUCTION Hereditary nephropathy is clinically characterized by the familial occurrence in successive generations of progressive haematuric nephritis and neural hearing loss. Hereditary nephropathy of Alport's syndrome (AS) and benign familial (recurrent) haematuria (BFH) are morphologically characterized by specific and diagnostically important thickening and splitting of lamina densa of the glomerular basement membranes. Those lesions can be recognized only by electron microscopy. Hereditary nephritis is usually present clinically with haematuria, and new mutations without a family history of haematuria. It is therefore important to differentiate hereditary nephritis from BFH and no familial haematuria. Thus, electron microscopy is essential in diagnosis of haematuria. OBJECTIVE The aim of this study was to describe, by light microscopy, constellation of renal alterations by which hereditary nephropathy can be recognized with high probability as well as to compare the diagnostic validity of the findings observed by light and electron microscopy in AS and BFH. METHOD We examined 48 renal biopsies of the patients with hereditary nephoropathies by light and electron microscopy. Tissue samples were fixed in buffered paraformaldehyde and embedded in paraffin for long-term preservation. For the electron microscopy analysis, the following fixation in 4% glutaraldehyde tissue was postfixed in 1% osmium tetroxide.Thereafter, the following dehydration procedure tissue slices were embedded in epon. RESULTS Our results demonstrated that the interstitial foam cells, foetal-like glomeruli, minimal glomerular abnormalities with stain less intense in basement membranes, mild irregular mesangial widening, focal thickening of Bowman's capsule, foci of dilatation tubules, tubular ectasia and atrophy, erythrocyte tubules casts were present in hereditary nephritis. Additionally, light microscopic biopsy findings in patients with BFH were either normal or revealed minor changes (e.g. increased mesangial matrix). All biopsies were reevaluated by electron microscopy and ultrastructural findings confirmed the diagnosis of hereditary nephropathies. CONCLUSION The findings observed by light microscopy represent an important step that leads to a definitive diagnosis of AS and BFH. The definitive diagnosis, however, depends on electron microscopy

TOKSIČNI STRES U DETINJSTVU I RIZIK ZA DUGOROČNE ZDRAVSTVENE POSLEDICE

Nepovoljna iskustva u detinjstvu (NID), uključujući zlostavljanje, zanemarivanje,disfunkcionalnu porodicu i druge stresne ili traumatične nedaće u detinjstvu, povezanesu sa dugoročnim negativnim zdravstvenim posledicama. Kao doprinoseći činilacu nastanku ovih posledica uključen je toksični stresni odgovor. Fiziološki odgovor nadelovanje stresora određen je višestrukim faktorima, uključujući trajanje i jačinu izloženosti,zaštitne faktore ili ranjivosti i razvojne činioce. Odgovor na delovanje stresoramože biti adaptacioni (fiziološki) ili maladaptacioni (patološki). U odgovoru na delovanjestresora nervni, endokrini i imunski sistem integrišu se u jedinstven neuro-endokrino-imunski sistem. Ako je izloženost stresoru vremenski ograničena i ukoliko osobaposeduje odgovarajuće mehanizme za suprotstavljanje, ovi sistemi podležu vremenskiograničenoj adaptaciji da bi se organizam vratio u stanje homeostaze. Međutim, dugotrajnaili jaka izloženost delovanju stresora može da prouzrokuje disregulaciju neuro-endokrino-imunskog sistema, oštećujući inhibiciju fidbekom i regulacione mehanizmei stvarajući maladaptacioni, toksični, odgovor na stres. Toksični stres može daprouzrokuje bilo suvišak bilo nedostatak hormona ili neurotransmitera indukovanihstresom, što opet, kada se doživi u toku senzitivnog perioda razvoja u detinjstvu, možeda bude ugrađeno u biološke sisteme u razvoju. Poremećena dostupnost hormona i neurotransmiteraizaziva trajne promene koje pogađaju brojne organske sisteme i funkcije,uključujući arhitekturu mozga, regulaciju endokrinog sistema i imunski odgovor.Promene u više organskih sistema, u sprezi sa genetičkom osetljivošću i epigenetičkomregulacijom, stavljaju osobu u rizik za negativne posledice po fizičko, mentalno i bihevioralnozdravlje u odraslom dobu

Chronic kidney disease during a 12-year period at tertiary health institution

Introduction. Chronic kidney disease (CKD) is a significant cause of morbidity and mortality in paediatric population. Objective. The aim of the study was analysis of aetiology, staging and associated complications of CKD at the time of diagnosis. Methods. Data of 97 patients (56 boys) of average age 7.8±5.8 years, referred for the first time to the Institute for Mother and Child Healthcare „Dr Vukan Čupić”, Belgrade in the period 1998- 2009, due to CKD, stage 2-5, were analysed. In each patient illness history was obtained, and physical examination, laboratory, X-ray and other investigations were performed according to the indications. CKD was classified according to the glomerular filtration rate into four grades: 2 - mild (60-90 ml/min/1.73 m2); 3 - moderate (30-60 ml/min/1.73 m2); 4 - advanced (15-30 ml/ min/1.73 m2); and 5 - terminal (<15 ml/min/1.73 m2). Results. The most frequent causes of CKD were congenital anomalies of the kidney and urinary tract (43.3%), followed by glomerular diseases (17.5%), hereditary kidney diseases (16.5%), metabolic diseases (7.2%) and other causes (15.5%). Mild CKD was found in 29.8%, moderate in 28.9%, advanced in 22.7%, and terminal in 18.6% children. Among patients with CKD stage 4 and 5, 75% of patients presented with acute renal failure, while 25% had earlier detected CKD (stage 1), but were not under regular follow-up. Associated complications included metabolic acidosis (63%), anaemia (60%), hypertension (42.3%), short stature (25.8%), renal osteodystrophy (13.4%) and cardiovascular diseases (7.2%). Conclusion. Congenital anomalies of the kidney and urinary tract are the leading cause of CKD in paediatric population. A significant proportion (41.3%) of patients had advanced and terminal CKD. In most patients CKD was diagnosed late and with associated complications

Iga nephropathy: clinical-morphologic correlation

IgA nephropathy is glomerular disease caracterized by the presencemorphologic changes as wella as the prognosis is in correlation with of IgA dominant or codominant imunoglobuline deposits in glomer-the amount of proteinuria. The prognosis is better in children. ular mesangium which can be demostrated by immunofluorescence. Clinical manifestations of IgA nephropathy in the majority of cases is hematuria which can be macro or mikroskopic, isolated or combined with proteinuria, which can be of nephrotic range. The prognosis o the disease is better if presented with haematuria. Intensity of????

Congenital thrombocytopenia with nephritis: The first case of MYH9 related disorder in Serbia

Introduction. The group of autosomal dominant disorders - Epstein syndrome, Sebastian syndrome, Fechthner syndrome and May-Hegglin anomaly - are characterised by thrombocytopenia with giant platelets, inclusion bodies in granulocytes and variable levels of deafness, disturbances of vision and renal function impairment. A common genetic background of these disorders are mutations in MYH9 gene, coding for the nonmuscle myosin heavy chain IIA. Differential diagnosis is important for the adequate treatment strategy. The aim of this case report was to present a patient with MYH9 disorder in Serbia. Case report. A 16-year-old boy was referred to our hospital with the diagnosis of resistant immune thrombocytopenia for splenectomy. Thrombocytopenia was incidentally discovered at the age of five. The treatment with corticosteroids on several occasions was unsuccessful. Although the platelet count was below 10 × 109/L, there were no bleeding symptoms. Besides thrombocytopenia with giant platelets, on admission the patient also suffered sensorineuronal hearing loss and proteinuria. The diagnosis was confirmed with immunofluorescence and genetic analyses. Conclusion. Early recognition of MYH9-related diseases is essential to avoid unnecessary and potentially harmful treatments for misdiagnosed immune thrombocytopenia, and also for timely and proper therapy in attempt to delay end-stage renal failure and improve quality of life. [Projekat Ministartsva nauke Republike Srbije, br. 175056 i br. 15079

Atypical presentation of cystic fibrosis: Obese adolescent with hypertension and pseudo-Bartter’s syndrome

Introduction. Infants with cystic fibrosis may fail to thrive despite recommended caloric intake because of electrolyte disurbances caused by salt depletion resulting in hypochloremic metabolic alkalosis or pseudo-Bartter's syndrome. In most patients reported symptoms began in infancy, but it may be an initial presentation of disease in a previously healthy adolescent. Case report. A 15-year-old boy was admitted for evaluation of recurrent episodes of malaise associated with dehydration and acute renal insufficiency. Laboratory analysis showed hypochloremic metabolic alkalosis with hyponatremia and hypokalemia. On admission the boy was obese, with body weight of 95.5 kg (> P97), height 174 cm (> P75), and body mass index of 31.2 kg/m2 (> P95). Physical examination was inconclusive. Blood pressure holter monitoring proved significant systolic hypertension. Routine urinalysis, protein and electrolyte levels in urine were normal. Plasma renin and aldosteron were normal. Sweat chloride concentration was 63 mmol/L. Genetic testing confirmed the diagnosis of cystic fibrosis. Conclusion. To our knowledge, this is the first reported case of atypical presentation of cystic fibrosis in an adolescent presented with pseudo-Bartter's syndrome and signs of obesity and hypertension. We suggest that every patient with hypochloremic metabolic alkalosis should be evaluated for cystic fibrosis

Infantile nephropathic cystinosis

Introduction. Infantile nephropathic cystinosis (INC) is a metabolic disorder due to impaired carrier-mediated transport of cystine out of cellular lysosomes. Objective. To examine the prevalence and clinical characteristics of INC in paediatric patients with end- stage renal disease (ESRD) in Serbia and give a recent statement of the disease. Methods. ESRD database of the Centre for Paediatric Renal Replacement Therapy (RRT) in Serbia was used to identify all patients with INC who started RRT before age of 19 years during the period January 1980 - December 2008; their records concerning clinical characteristics, therapy and outcome were evaluated. Results. Only three of 298 paediatric patients with ESRD had INC. The first signs of the illness were recognised during infancy. Fancony syndrome was diagnosed in the second year, but the diagnosis of cystinosis was delayed at mean 6 years. ESRD occurred in the first decade of life. All patients under- went cadaver kidney transplantation. At the end of the study period all patients were alive. A 31-year-old female patient was on maintenance chemodialysis due to graft failure after functioning for 11 years. She was growth retarded, single, unemployed, with severe signs of renal dystrophy. Two male patients (14.3 and 14.7 years old) had normal graft function, normal education, and good quality of life, although they were also severe growth retarded. Conclusion. The prevalence of infantile nephropathic cystinosis is low in Serbia. The diagnosis of cystinosis was delayed in all patients, although they exhibited the typical course of the disease

Corticosteroid-responsive nephrotic syndrome in children with myelodysplastic syndromes

Several reports have documented various forms of glomerular diseases in adults with myelodysplastic syndromes (MDS), but similar reports in children are lacking. We describe two children with MDS-associated with steroid-responsive nephrotic syndrome (NS). Patient 1, who had MDS with myelofibrosis, presented also hepatosplenomegaly, pancytopenia, chronic hepatitis, moderate proteinuria, hypocomplementemia and elevated ANA titer. During initial prednisone treatment proteinuria markedly diminished and partial but transient haematological improvement occurred. Relapse subsequently occurred that was manifested by overt NS and pancytopenia. High doses of prednisolone led to remission of the renal disease but haematological remission did not occur. Persisting pancytopenia and repeated infections terminated in sepsis, two years after the onset of MDS. Patient 2, who had refractory anemia with clonal monosomy 19, manifested bowel disease, hepatospleno- megaly, anaemia and non-organic specific autoantibodies. Prednisone led to both clinical and haematological remission. Haematologic disease relapsed 12 months later, when nephrotic-range proteinuria, haematuria and mild azotaemia were also found. Corticosteroid treatment led to long-lasting renal and haematologic remission, maintained by a small dosage of prednisone. In both patients renal biopsy findings were consistent with those seen in idiopathic NS. A Medline search disclosed 16 cases of glomerulopathy in the course of MDS in adult patients. Clinical features included NS, usually accompanied by renal insufficiency with either acute, chronic, or rapidly progressive glomerulonephritis. On biopsy, membranous nephropathy, crescentic or mesangial proliferative glomerulonephritis and AL amyloidosis, were found. We conclude: (1) that glomerular disease may be present and should be searched for in patients with MDS; (2) that MDS can be added to the list of rare conditions associated with corticosteroid-responsive NS in children