Immune-mediated hemolytic anemia in pediatric renal transplantation

The aim of the study was to demonstrate clinical course of the first reported cases of PLS in pediatric kidney transplantation and therapeutic outcome for such condition using a combination of high-dose corticosteroid and tacrolimus. We report a single case (a nine-year-old Thai boy) with end-stage kidney disease secondary to obstructive uropathy developed immune-mediated hemolytic anemia from the PLS at second week after a pre-emptive living-related kidney transplantation. The alloimmune hemolysis was a result of anti-B antibodies, derived from blood group O-donor lymphocytes. Using a combination of high-dose corticosteroid and a substitution of cyclosporin with tacrolimus, there was no further hemolysis although the anti-B antibodies remained detectable until the eighth week post-transplantation. An impairment of the graft function because of hemoglobinuria was resolved after the hemolysis was stopped. The alloimmune hemolysis caused by PLS in pediatric kidney transplantation could be controlled with a combination of high-dose corticosteroid and tacrolimus.     

The role of DMSA renal scintigraphy in the first episode of urinary tract infection in childhood

Objective

The role of dimercaptosuccinic acid (DMSA) renal scintigraphy in the first episode of urinary tract infection (UTI) has been the subject of debate for many years. The aim of this study was to evaluate the relationship of voiding cystourethrography (VCUG), renal ultrasonography and DMSA renal scintigraphy and to detect renal parenchymal changes by performing DMSA renal scintigraphy at 6 months after the first episode of UTI.

Methods

A prospective study was conducted in 67 hospitalized children (46 boys, 21 girls). Mean age of the patients was 0.97 ± 1.57 years (0.02–7.26 years). All children received VCUG, renal ultrasonography and DMSA renal scintigraphy. DMSA renal scintigraphy was performed at 1 and 6 months after UTI.

Results

Of 67 children, 17 (25.4 %), 23 (34.3 %) and 20 (29.9 %) had vesicoureteral reflux (VUR), abnormal renal ultrasonography and abnormal DMSA renal scintigraphy, respectively. Unilateral hydronephrosis had a significant correlation with VUR at p value 0.024. In renal units, abnormal renal ultrasonography and hydronephrosis had significant correlations with VUR at p values 0.039 and 0.021, respectively. In patients and renal units, hydronephrosis had no significant correlation with abnormal DMSA renal scintigraphy at 1 month after UTI. However, abnormal renal ultrasonography and VUR had significant correlations with abnormal DMSA renal scintigraphy at p values 0.022 and <0.001 in patients and at p values 0.024 and <0.001 in renal units, respectively. Both in patients and renal units, VUR (Grade I–III) had no significant correlation with abnormal DMSA renal scintigraphy. However, severe VUR (Grade IV–V) had significant correlations with abnormal DMSA renal scintigraphy at p values <0.001 and <0.001, respectively. Seventeen patients underwent DMSA renal scintigraphy at 6 months after UTI. In addition, 15 (88.2 %) developed persistent renal scarring.

Conclusion

Abnormal renal ultrasonography and severe VUR identify renal parenchymal changes. DMSA renal scintigraphy in the first episode of UTI should be carried out in those patients. Abnormal DMSA renal scintigraphy at 1 month after UTI has a tendency to persist.     

Combined renin angiotensin blockade in childhood steroid‐resistant nephrotic syndrome

Background: Reduced proteinuria results in delayed deterioration of renal function and remission of proteinuria predicts a good long‐term prognosis in steroid‐resistant nephrotic syndrome (SRNS). The aim of this study was to analyze the effects of the combined angiotensin‐converting enzyme inhibitor and angiotensin II receptor blocker in reducing proteinuria in SRNS. Methods: A prospective study of eight patients with SRNS was conducted at the Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University from September 2003 to December 2007. Enalapril was given at 0.1 mg/kg/day and was increased by 0.1 mg/kg/day every 4 weeks up to 0.6 mg/kg/day (maximum 40 mg/day) and 1 mg/kg/day of losartan was added for 4 weeks and stepped up to 2 mg/kg/day (maximum 100 mg/day) for another 4 weeks. Results: There were five boys (62.5%) and three girls (37.5%). The mean age at diagnosis was 8.3 ± 4.1 years (range 2.05–13 years) and age at enrollment was 11.7 ± 3.8 years (range 6–16 years). Renal histology revealed seven focal segmental glomerulosclerosis and one immunoglobulin M nephropathy. The results showed significant reduction on mean spot urine protein : creatinine ratio from 9.6 ± 2.3 to 3.6 ± 1.6 (P < 0.05) and 24‐h urine protein from 182.8 ± 59.6 to 28.7 ± 8.2 mg/m²/h (P < 0.05). Urine protein reduction ratio at the end of the study was 50% (P= 0.08). Serum cholesterol, albumin, potassium, blood pressure and renal function had no significant change. No clinical and laboratory side‐effects were reported. Conclusion: Combined high‐dose angiotensin II receptor blocker to high‐dose angiotensin‐converting enzyme inhibitor therapy is safe and effective in reducing proteinuria in childhood SRNS. However a large‐scale study should be conducted to validate this result.     

Gene expression in early ischemic renal injury: clues towards pathogenesis, biomarker discovery, and novel therapeutics

Acute renal failure (ARF) represents a common and serious problem in clinical medicine. Renal ischemia-reperfusion injury (IRI) is the major cause of ARF in the native and transplanted kidney. Several decades of research have provided successful therapeutic approaches in animal models, but translational efforts in humans have yielded disappointing results. The major reasons for this include a lack of early markers for ARF (and hence a delay in initiating therapy), and the multi-factorial nature of the disease. This review focuses on the use of cDNA microarrays to elucidate the molecular genetic mechanisms underlying tubule cell apoptosis, and to identify novel biomarkers for early renal IRI. Also presented is a comparative temporal analysis of cDNA microarray results from mature kidneys following IRI and during normal nephrogenesis. Molecular genetic evidence for the notion that regeneration recapitulates development in the kidney, and that injured tubule cells possess the capacity to de-differentiate to the earliest stages of development, is presented. The implications of these findings to the ability of the kidney to repair itself and potential strategies for accelerating recovery are briefly discussed.