Nurdan Kural

IGF-1, IGFBP-3, VEGF and MMP-9 levels and their potential relationship with renal functions in patients with compensatory renal growth

Background:  Mechanisms of compensatory renal growth (CRG) still remain a mystery. Various growth factors, including growth hormone, insulin‐like growth factor‐1 (IGF‐1) have been implicated in different forms of CRG.

Co-existence of renovascular hypertension, polyarteritis nodosa, antiphospholipid syndrome and methylenetetrahydrofolate reductase mutation

We present a hypertensive child with a co‐existence of polyarteritis nodosa, anti‐phospholipid antibodies (aPL), methylenetetrahydrofolate reductase (MTHFR) mutation and increased lipoprotein a level. Elevated renin, aldosterone and aPL levels, micro‐aneurysms, occlusion and thrombosis at left and right renal artery were found. Anti‐hypertensive agents, prednisolone and pulse cyclophosphamide therapy were started and a stent was inserted in the left renal artery. Two months later, brain magnetic resonance imaging/magnetic resonance imaging angiography showed acute infarct area of the left parietofrontal lobe and middle cerebral artery stenosis. We found bilateral peripheral neuropathy, persistent aPL and elevated Lp(a) level and heterozygous A1298C/MTHFR mutation. Intravenous immunoglobulin and low‐molecular‐weight heparin treatment was added. In conclusion, our observation suggests that in patients with systemic vasculitis, such as polyarteritis nodosa, aPL are probably associated with greater thrombotic risks. The investigation of the LP(a) levels and MTHFR mutations as a synergic pro‐coagulant effect might also be considered for determining patients with vasculitis at risk for severe thrombotic events.

CD19 + CD23+ B cells, CD4 + CD25+ T cells, E-selectin and interleukin-12 levels in children with steroid sensitive nephrotic syndrome

Background and methodsSoluble-lymphocyte subsets (sCD19 + CD23+ B cells and sCD4 + CD25+ T cells), soluble-adhesion molecules (sE-selectin) and interleukin-12 (sIL-12) were assayed to evaluate the pathogenesis of steroid sensitive nephrotic syndrome in 48 patients diagnosed with steroid sensitive nephrotic syndrome (SSNS) in active (AS) and remission stages (RS).ResultsThe ratios of soluble CD19 and sCD19 + CD23 increased in patients with AS with respect to the patients with RS and controls (p < 0.05). Increased sCD19 + CD23 ratios were preserved in the patients with RS when compared with the controls (p < 0.05). Moreover, the ratios of sCD4 + CD25 lymphocyte subsets were not significantly different among the groups. Similarly, serum sIL-12 levels were not considerably disparate between the AS and RS. Serum sE-selectin levels were higher in the patients with AS relative to the controls (p < 0.01) and RS (p < 0.05). No significant correlations were noted between sE-selectin and lymphocyte subset ratios, serum sIL-12 and immunoglobulin levels. There was a positive correlation between sE-selectin, triglyceride (r = 0.757, p < 0.0001) and cholesterol (r = 0.824, p < 0.0001) levels in patients with the AS.ConclusionThe present results indicate that the patients with SSNS appear to have abnormalities in sCD23 + CD19+ cells, defect in T regulatory cell activity, and injury in endothelial cells as indicated by the presence high sE-selectin. These abnormalities might play a role in the pathogenesis of nephrotic syndrome. sIL-12 seems to have no role in pathogenesis of nephrotic syndrome reflecting normal Th1 response.

Atypical hemolytic uremic syndrome associated with group A beta hemolytic streptococcus

Sirs, We read with interest the article by Shepherd et al. [1], entitled “Hemolytic uremic syndrome associated with group A beta hemolytic streptococcus.” The authors reported a 9-year-old white male who developed hemolytic uremic syndrome (HUS) with group A beta hemolytic streptococcus-positive diarrhea. We would like to report a similar case of group A beta hemolytic streptococcus with HUS but with no diarrhea. A 6-year-old female was transferred to our hospital with a history of pallor, edema of the eyes and lower extremities, fever, fatigue, and oliguria. She had no acute diarrheal prodrome. There was no familial history for HUS. On admission her temperature was 37.5oC, heart rate 104 beats per minute, and blood pressure 110/50 mm/ Hg. She had edema and petechia. Urinalysis revealed a specific gravity of 1.020, pH 7, 3+ protein and blood, and low-grade microscopic hematuria [8–9red blood cells (RBC) per high-power field]. The serum fibrinogen level, prothrombin time (PT), and activated partial thromboplastin time (aPTT) were normal, but D-dimer was 26.94 g/l. Total bilirubin was 1.9 mg/dl (indirect bilirubin 1.6 mg/dl). C3 was 66.6 mg/dl (normal 90–180 mg/ dl) and C4 was 12.8 mg/dl (normal 7–40 mg/dl). Blood cultures obtained from different sites showed growth of a group A beta hemolytic streptococcus. The hemoglobin level decreased to 5.5 g/dl on the 2nd day and the blood smear showed fragmented RBC, helmet cells. A high reticulocyte count (8%) and low haptoglobin level (5.83 mg/dl) suggested hemolytic anemia. Thrombocytopenia (platelet count of 9,000/mm) and renal failure developed with a blood urea nitrogen level of 87 mg/dl and a serum creatinine level of 1.6 mg/dl. These findings indicated HUS. The patient was treated with fresh-frozen plasma, intravenous cefepime (150 mg/kg per day), lowdose heparin, fluid, and diuretics. While in hospital, she had high blood pressure that was treated with prazosin. Renal function was not re-established, her urine output was less than 1 ml/kg per hour, and peritoneal dialysis was started. In conclusion, our patient showed quite different laboratory findings, pathogenetic mechanism, treatment strategies, and outcome from that reported by Shepherd et al. [1]. In this patient, the D-dimer level was high with a normal serum fibrinogen level, PT, and aPTT. As in our patient, patients with HUS, normal PT/aPTT and fibrinogen levels with increased D-dimer have been reported not to have disseminated intravascular coagulation [2, 3]. This may be because children with HUS with normal PT/ aPTT do not have increased tissue factor activity and patients with HUS and other secondary thrombotic microangiopathies have increased plasminogen activator inhibitor-1 antigen levels [4]. The release of inflammatory mediators such as tumor necrosis factor-a (TNF-a), interleukin-1 (IL-1), and elastase in the presence of group A beta-hemolytic streptococcus bacteremia may play a role in the pathogenesis of HUS. TNF-a, IL-6, and IL-8 are increased in patients with HUS [5]. A major mechanism of cell death and apoptosis is related to bacteremia. One pathway involves the binding of TNF produced in response to infection by macrophages and T cells to its receptor (TNFR1). Another pathway involves the Fas/ Fas-ligand (Fas-L) system [6, 7]. Our patient was treated with cefepime because of Streptococcus pneumonia bacteremia associated with HUS [8]. Hypocomplementemia typically is found in sporadic D forms of HUS and in most parts of the world atypical HUS is characterized by a high incidence of recurrence, end-stage renal disease, and death. Low C3 levels predict a poor outcome [9, 10, 11]. The C3 levels of our patient were low, her renal function did not show complete recovery, and she was treated with continuous ambulatory peritoneal dialysis. A reply to this letter is available at http://dx.doi.org/10.1007/ s00467-004-1530-0

IgG1 deficiency and high IgA level with juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children, but its immunopathogenic mechanism remains unclear. Generally, JIA is considered as T-cell mediated, but contribution of B cells is debatable. This report describes a 6-year old patient with IgG1 deficiency and high IgA level with JIA. He had had bilateral pains in distal interphalangeal, knee, and elbow and right hip joints, with morning stiffness for 2 years, bilateral swelling in upper distal interphalangeal, knee and elbow joints, and restricted motion of joints. His family noted that he had recurrent sinopulmonary infections. No familial chronic diseases, such as ankylosing spondylitis and SEA syndrome, were present. Haematological, biochemical, urine analysis and renal-function test results were normal. Erythrocyte sedimentation rate (ESR) was 15 mm/h. Rheumatoid factor, anti-nuclear antibody, anti-IgA antibodies and human leucocyte antigen B-27 were negative. C3 was 112 mg/dl and C4 was 29.1 mg/dl. Levels of immunoglobulins (Igs) (M, A, G, G1, G2, G3, G4,), with normal ranges, were 65.5 (4–304), 701 (82–453), 366 (751–1560), 182 (330–1065), 145 (56,5–345), 31.4 (7.5–125.6), and 7.32 (1.8–115.5), respectively, as milligrammes per decilitre. Lymphocyte subpopulation values were normal [CD3 65% (48–79%), CD4 34% (25–59%), CD8 29% (10–42%), CD19 23% (8–44%), CD56 9% (10–19%) and CD4 CD25 4,6% (1–8%)]. All the tests were done four times during the follow-up period. Low IgG1 and high IgA levels were persistent in four different blood samples. Based on these findings, polyarticular JIA with IgG1 deficiency and high IgA level was diagnosed. The patient was successfully treated with tolmetin sodium 20 mg/kg per day. No destructive problem occurred during the follow-up period. Arthritis is considered to be related to humoral immune deficiency [1, 6]. Mechanisms of IgG subclasses deficiency with JIA are unclear. Possible mechanisms include genetic background, lack of some interleukins and CD86 and/or β2 adrenergic receptor stimulation [6]. The most common types of arthritis with humoral immune deficiency are benign, aseptic, and characteristically non-erosive polyarthritis [4]. On the basis of our findings, we conclude that selective IgG1 deficiency with JIA does not result in disability and has no systemic onset. It also could be seronegative, polyarticular, and have a good response to non-steroid anti-inflammatory drugs, besides having a low ESR. IgA has been implicated in the pathogenesis of arthritis due to immune complex formation. The following evidence might indicate the causes of high serum IgA levels: (1) that gene expression of transforming growth factor beta, a known cytokine to increase IgA production by human splenic B cells, is enhanced in mononuclear cells from synovial fluid and (2) that iron deposition is found in rheumatoid arthritis (RA) synovia, and high serum IgA levels are found in iron overload conditions such as thalassaemia intermedia. [5]. High IgA levels with RA were found to increase ESR, and microscopic haematuria, and both distal interphalangeal joint involvement and unilateral sacroiliitis, may develop [3]. However, our patient had unilateral sacroiliitis but normal ESR and urine analysis. Badcock et al. thought that IgA does not affect the Eur J Pediatr (2007) 166:1179–1180 DOI 10.1007/s00431-006-0360-4

Acute renal failure in two infants due to ureteropelvic fungi balls.

Fungal infections occur in infants and may be responsible for serious and occasionally fatal disease.1 As the survival rates for premature infants improve, they are more susceptible to opportunistic fungal infections. Because of the use of intravascular catheters, parenteral nutrition and broad-spectrum antibiotics are predisposing factors for the development of fungal infections, especially in those premature infants who have poor host defenses against infections.1 Renal candidiasis in infants is a potential fatal complication of systemic candidiasis or ascending candidiasis.2 The clinical and sonographic features of two prematurely born infants aged 2/2 and 4/2 months with renal candidiasis were presented. It is suggested that in any infant with a clinical suspicion of renal candidiasis, renal ultrasonography should be performed to facilitate early diagnosis and treatment of renal fungal disease.