Gülay Demircin

Efficacy of colchicine therapy in amyloid nephropathy of familial Mediterranean fever

Abstract.The aim of this study was to investigate the effect of colchicine therapy on the outcome of amyloid nephropathy of familial Mediterranean fever (FMF) in childhood. The diagnosis of amyloidosis type AA was confirmed by renal biopsy in 38 patients. During a mean follow-up period of 30.5xa0months (range 6–88xa0months), the patients received colchicine therapy. While 24 of these patients were compliant with the treatment, 14 patients remained non-compliant. Of the 24 compliant patients, 19 had normal renal function at the onset; in 13 the proteinuria improved, in 5 patients it remained stable, and in 1 patient it deteriorated from a proteinuric to nephrotic stage. Partial resolution of amyloidosis was demonstrated by repeat renal biopsy in 1 patient who showed complete resolution of proteinuria. In contrast, none of 14 non-compliant patients improved, and while only 1 patient was in renal failure initially, 10 patients deteriorated to renal failure during the follow-up period. The presence of tubulointerstitial injury at presentation adversely affected the prognosis. In conclusion, when used appropriately, colchicine can improve proteinuria and prevent chronic renal failure in patients with amyloid nephropathy of FMF. The presence of renal failure or tubulointerstitial injury at presentation and non-compliance with therapy are the factors decreasing the success of therapy.

A one-center experience with pediatric percutaneous renal biopsy and histopathology in Ankara, Turkey.

In this study we evaluated the indications, complications, and the spectrum of histopathological results of percutaneous renal needle biopsy (PRNB) performed in our clinic. Between June 1990 and December 2006, 679 PRNBs were performed on native kidneys of 614 children (304 boys, 310 girls) with a mean age of 10.4xa0years. Most frequent indications for PRNB were nephrotic syndrome (47%), hematuria, and/or proteinuria (15.9%), acute renal failure (14.6%) and complex renal manifestations (18.9%). The overall complication rate was 15.2%. The most common complications were perirenal hematoma (12.4%) and macroscopic hematuria (2.6%). The most frequent histopathological group of diseases were glomerulopathies; these were diagnosed in 376 patients (61.2%) and included membranoproliferative glomerulonephritis (11.1%), mesangial proliferation (10.7%), diffuse proliferative glomerulonephritis (7.7%), and focal segmental glomerulosclerosis (7.3%) as the most frequent. The second most frequent group of histopathology was manifestations secondary to systemic diseases; these were shown in 195 patients (31.8%). Amyloidosis (11.4%) and Henoch–Schönlein nephritis (9.9%) made the majority of this group. In conclusion, our study demonstrated that PRNB is a safe procedure with usually transient complications showing the most frequent renal diseases that cause diagnostic and therapeutic difficulties for pediatric nephrologists.

Genetic risk factors of amyloidogenesis in familial mediterranean fever

Background/Aims: Evaluation of the risk factors, and phenotype-genotype correlation of familial Mediterranean fever (FMF) gene (MEFV) and serum amyloid A1 (SAA1) gene polymorphisms in renal amyloidosis. Methods: We investigated MEFV and SAA1 genotypes (α, β, and γ isoforms) in 50 FMF patients and 50 healthy children. Tel-Hashomer criteria were used for the diagnosis and severity scoring of FMF. Results: The most common MEFV mutation and SAA1 genotype were M694V/M694V (n = 26/50) and SAA1 α/α (n = 26/50), respectively. Positive family history for amyloidosis was significantly higher (p < 0.001) with more severe clinical course (p = 0.006) in the amyloidosis group than the non-amyloid group. In M694V/M694V mutation, erysipelas-like skin erythema (p = 0.029), arthritis (p = 0.004), arthralgia (p < 0.001) were significantly more frequent with higher severity scores (p = 0.008) than the patients with other mutations. Comparison of the SAA1 α/α genotype with other genotypes revealed more frequent arthritis (p = 0.003) in the SAA1 α/α genotype. In amyloidosis group patients having both M694V/M694V and SAA1 α/α genotypes were the largest subgroup (n = 14, p < 0.001). Logistic regression analysis for amyloidosis corrected risk revealed a 1.2 times increase in M694V/M694V, a 2.4 times increase in SAA1 α/α genotypes and a 2.5 times increase when both are together. Conclusion: Positive family history for amyloidosis and presence of SAA1 α/α genotype in M694V/M694V mutation may predispose to amyloidosis by increasing the clinical severity. Therefore, in such children early colchicine treatment might be recommended even if they are asymptomatic.

An unusual case of ANA negative systemic lupus erythematosus presented with vasculitis, long-standing serositis and full-house nephropathy

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that may affect any organ of the body. We report here an unusual case of seronegative SLE presented as vasculitis with rash, lower gastrointestinal system bleeding and acute renal failure. The patient was a 13-year-old boy, with abdominal distention, pretibial edema, arthritis and petechia on bilateral ankles. He had deteriorated renal functions (creatinine 1.65xa0mg/dl), hypoalbuminemia (1.6xa0g/dl) and hypocomplementemia with nephrotic range proteinuria and hematuria. He developed pleural effusion and peritonitis. Serum ANA, anti dsDNA, p ANCA, c ANCA, anticardiolipin IgM and IgG titers were negative. A renal biopsy was performed which revealed diffuse proliferative glomerulonephritis with full-house staining pattern in immunofluorescent microscopic examination suggesting Class IV Lupus Nephritis. He was administered a total of six courses of monthly intravenous pulse methyl prednisolone, dipyridamole, oral cyclophosphamide followed by azothiopirine and oral prednisolone therapy. The renal functions and serum albumin levels turned normal but peritonitis persisted and disappeared after the third pulse steroid therapy. In conclusion, we presented this patient to remind the possibility of SLE in such seronegative patients with unusual findings in order to avoid the delay in the management of this disease with high mortality and morbidity if not treated. Full-house nephropathy is an important clue especially for the diagnosis of ANA negative SLE.

Erythrocyte superoxide dismutase activity and plasma malondialdehyde levels in children with Henoch Schönlein purpura

Reactive oxygen molecules (ROM) have been suggested to contribute to many pathological conditions including vasculitides and renal diseases. In the present study we measured the activity of superoxide dismutase (SOD) as an antioxidant enzyme in red blood cells and the level of malondialdehyde (MDA), which is a product and an indicator of lipid peroxidation, in the plasma of 16 children (7M, 9F) with Henoch Schönlein purpura (HSP) at the onset of the disease (SOD 1 and MDA 1) and at the remission period (SOD 2 and MDA 2). The results were compared with the results of 17 healthy children studied as a control group. There was no significant difference for SOD activities between the patients in each period and the control group (p > 0:05). There was a statistically significant difference between MDA 1 and MDA 2 levels (p < 0:01), each of which were also significantly different from the MDA levels of control group (p < 0:001 and p < 0:01, respectively). The effect of ROMs on different clinical conditions of HSP was also examined and lipid peroxidation was found to be increased more in patients with renal involvement. It is concluded that oxidant stress especially lipid peroxidation plays an important role in the pathogenesis of HSP and in development of renal injury.

Hemolytic uremic syndrome triggered with a new pandemic virus: influenza A (H1N1)

Sirs, In April 2009, a new strain of human influenza A (H1N1) virus causing human disease was identified. Based on evidence of community transmission of this new strain from person to person in more than one of its regions, the World Health Organization (WHO) declared a pandemic in June 2009. We present a case of recurrent hemolytic uremic syndrome (HUS) in a patient who was admitted with a new attack triggered by influenza A (H1N1) virus infection. We also discuss the progression of the disease. A 15-year-old girl was admitted to our hospital in December 2009 with complaints of throat pain, fever, and nasal drip, followed by weakness, vomiting, and nonbloody diarrhea lasting for a few days. There were people with similar complaints in her vicinity. The patient had first been admitted to our hospital with HUS at the age of 4 years; at this time, her admittance was followed by 2 days of non-bloody diarrhea. She had completely recovered without dialysis treatment but had recurrences at 12, 13, and 14 years of age. However, during the attacks her serum creatinine levels did not exceed 2.65 mg/dl (Fig. 1). On physical examination she was pale and showed signs of dehydration, pharyngeal hyperemia, and postnasal discharge. Her arterial tension was 150/100 mmHg. Laboratory tests indicated severe anemia with findings of intravascular hemolysis and thrombocytopenia. She had 2+ proteinuria and microscopic hematuria on urinalysis. Serum creatinine was 5.1 mg/dl; blood urea nitrogen, 97 mg/dl; uric acid, 9.7 mg/dl; total protein, 6.6 g/dl; albumin, 3.3 g/dl; total bilirubin, 2.1 mg/dl; indirect bilirubin, 1.9 mg/dl; serum aspartate transaminase, 129 U/l; alanine transaminase, 27 U/l; lactate dehydrogenase, 847 U/l. Serum haptoglobin was <5 mg/dl (range 36–195 mg/dl). Prothrombin and activated partial thromboplastin times were normal. Throat, stool, urine, and blood cultures were negative. Serum complement 3 (C3) level was 0.979 g/l (normal range 0.83–1.77 g/l), C4 level were 0.256 g/l (normal range 0.12– 0.4 g/l). Serum antinuclear antibodies (ANA), anti-doublestranded (ds)DNA, and pand c-antinuclear cytoplasmic antibody titers were negative. She was diagnosed with HUS. Viral PCR analysis of the nasopharynx swab for the detection of influenza A (H1N1) was positive and believed to be the triggering factor of the HUS. She was started on oseltamivir therapy with an adjusted dose according to the degree of renal failure. Dialysis treatment was not initiated on the first day due to her history of improving without dialysis treatment in previous HUS attacks. She was given daily fresh frozen plasma infusions together with erythrocyte and platelet transfusions when necessary. Her serum creatinine value decreased the following day. Six days later, her serum creatinine level had decreased to 3.2 mg/dl, her uric acid level was 8.8 mg/dl, and her hemoglobin had increased to 9.3 g/dl and platelets to 48,000/mm. Daily fresh frozen plasma therapies were sustained until her renal function was normal. Oseltamivir treatment was completed at 7 days. On the 14th day following treatment initiation, her serum creatinine was 0.8 mg/dl, and all of her laboratory test results were normal. Atypical HUS (aHUS) has a poor prognosis, with approximately 50% of patients progressing to end-stage renal disease (ESRD). Several studies have confirmed a genetic predisposition to this disease that involves factors A. Çaltik (*) : S. G. Akyüz :Ö. Erdogan :G. Demircin Pediatric Nephrology Department, Dr Sami Ulus Children Hospital, Ankara, Turkey e-mail: acaltik@hotmail.com

Acute necrotizing tubulointerstitial nephritis due to systemic adenoviral infection

Abstractu2002To date, all the reported cases of acute necrotizing tubulointerstitial nephritis (TIN) secondary to systemic adenovirus infection have occurred in individuals with primary or secondary immunodeficiency, and have resulted in renal failure and death. We present the case of a 12-year-old, immunologically competent girl who developed acute necrotizing TIN with acute renal failure (ARF), hepatitis and meningoencephalitis secondary to a systemic adenoviral infection who completely recovered with supportive care.

A boy with consecutive development of SLE and Wegener granulomatosis.

An 11-year-old boy with consecutive development of systemic lupus erythematosus (SLE) and Wegener granulomatosis (WG) is presented. He was first admitted to the hospital with the findings of SLE, including crescentic glomerulonephritis, Coombs′ test-positive hemolytic anemia, hypocomplementemia, antinuclear antibody (ANA) positivity, and elevated levels of anti-double-stranded (ds) DNA antibodies. He was treated successfully with steroids, cyclophosphamide, and peritoneal dialysis. One month after his discharge he developed an apparent viral infection. Three weeks afterwards he was readmitted with the findings of lower respiratory tract involvement, maxillary sinusitis, nasal septum perforation, p- and c-antineutrophil cytoplasmic antibody (ANCA) positivity, but normal complement, ANA, and anti-ds DNA levels, suggesting the diagnosis of WG. He did not respond to anti-infectious and immunosuppressive treatment, and he died of Pseudomonas sepsis.

Rare presentation of cystinosis mimicking Bartter's syndrome: reports of two patients and review of the literature.

We present here two girls with cystinosis initially diagnosed as Bartter syndrome. Both cases were admitted with hypokalemic, hypochloremic alkalosis. Their proximal tubular functions, ophthalmologic and bone marrow examinations were normal. They were started on therapies with the diagnosis of Bartter syndrome. The first patient developed signs of rickets, and the second patient was lost to follow-up and readmitted with chronic renal failure. On reevaluation cystine crystals were detected in cornea and bone marrow aspirates of both patients. We aimed to remind the rare presentation of cystinosis with metabolic alkalosis mimicking Bartter syndrome by these two cases and review the literature.

Henoch Schönlein purpura and amebiasis

Abstract The pathogenesis of Henoch Schonlein purpura (HSP) is unknown but is believed to result from an immune complex reaction to various antigenic stimuli, such as infectious agents. However, its association with Entamoeba histolytica has not been reported before. We present an 11 ‐year‐old boy with HSP, confirmed by the demonstration of leukocytoclastic vasculitis from skin and diffuse endocapillary proliferative glomerulonephritis, together with immunoglobulin A and complement component C3 deposition from renal biopsies. Cysts and trophozoites of Entamoeba histolytica were detected from the stool of the patient at the same time and disappeared after the treatment with metranidasole. The temporal association of these two disorders is either coincidental or due to a causal relationship between them.