Pyung Kil Kim

Analysis of renal biopsies performed in children with abnormal findings in urinary mass screening

BACKGROUND School urinary mass screening tests are performed to make early diagnosis and provide proper treatment for chronic renal diseases. However, very few systemic analyses or studies have been reported regarding final diagnosis made on children with abnormal urinary screening results. AIM To study the cases of renal biopsy in children detected in urinary screening. METHODS We retrospectively analysed 461 cases of renal biopsy performed on children referred to us with abnormal school urinary mass screening results who satisfied indications for renal biopsy. RESULTS Pathologically abnormal findings were observed in 285 (61.8%) patients. Thin glomerular basement membrane disease was detected in 127 (27.5%) cases and IgA nephropathy in 121 (26.2%) cases. Among those 461 children, microscopic haematuria was observed in 289 (62.7%) patients, proteinuria in nine (2.0%), and both in 163 (35.4%). In addition, a statistically higher rate of pathological abnormalities on renal biopsy was noted in the group with microscopic haematuria combined with proteinuria and also in cases with more severe haematuria. CONCLUSION School urinary mass screening has greatly contributed to diagnosing chronic renal diseases. Continuous medical observation is required when abnormal urinalysis is observed, and a more aggressive medical approach such as renal biopsy should also be performed if necessary.

Successful use of cyclosporin A in severe Schönlein–Henoch nephritis resistant to both methylprednisolone pulse and azathioprine

Schönlein–Henoch nephritis (SHN) usually presents with micro-haematuria or mild proteinuria but can be associated with heavy proteinuria and nephrotic or acute nephritic syndrome. Although the treatment of SHN is still under debate, it has been suggested that cyclosporin A (CsA) may be beneficial in children with severe SHN, as reported by Ronkainen et al. (Pediatr Nephrol 18:1138–1142, 2003) and Someya et al. (Pediatr Int 46:111–113, 2004). However, histological effects of CsA on severe SHN had not been evaluated in their evaluations. We report the successful use of CsA in a male patient with severe SHN with nephrotic-range proteinuria, who failed to respond to methylprednisolone pulse and azathioprine therapy.

Effects of Cyclosporin A Therapy Combined with Steroids and Angiotensin Converting Enzyme Inhibitors on Childhood IgA Nephropathy

To evaluate the effects of cyclosporin A (CyA) on clinical outcome and pathologic changes in children with IgA nephropathy (IgAN), we retrospectively evaluated 14 children (mean age 8.9±2.9 yr; eight males, six females) who were treated with CyA and steroids. The starting dose of CyA was 5 mg/kg per day, and the drug level was maintained at 100-200 ng/mL. The mean CyA level was 183.8±48.3 ng/mL (range 120.7-276.0 ng/mL) and the mean duration of CyA therapy was 10.9±1.9 months (range 8-12 months). After CyA therapy the mean 24 hr urinary protein excretion declined from 107.1±35.1 mg/m2/hr to 7.4±2.4 mg/m2/hr (P<0.001) and serum albumin increased from 3.3±0.6 g/dL to 4.3±0.3 g/dL (P<0.001). At a follow-up biopsy the histological grade of IgAN was improved in seven (50%) of the 14 patients, remained the same in three (21%), and was aggravated in four (29%). Serum creatinine, creatinine clearance, and blood pressure did not differ before and after CyA therapy. Two patients (14%) showed CyA-induced nephrotoxicity at the second biopsy. Our findings indicate that CyA therapy may be effective in reducing proteinuria and regressing renal pathology in a subset of children with IgAN.

Outcomes of Peritonitis in Children on Peritoneal Dialysis: A 25-Year Experience at Severance Hospital

Purpose Relatively little is known on the microbiology, risk factors and outcomes of peritoneal dialysis (PD)-associated peritonitis in Korean children. We performed this study in order to evaluate the incidence, treatment and clinical outcomes of peritonitis in pediatric PD patients at Severance Hospital. Materials and Methods We analyzed data from 57 PD patients younger than 18 years during the period between June 1, 1986 and December 31, 2011. The collected data included gender, age at commencement of PD, age at peritonitis, incidence of peritonitis, underlying causes of end stage renal disease, microbiology of peritonitis episodes, antibiotics sensitivity, modality and outcomes of PD. Results We found 56 episodes of peritonitis in 23 of the 57 PD patients (0.43 episodes/patient-year). Gram-positive bacteria were the most commonly isolated organisms (40 episodes, 71.4%). Peritonitis developed in 17 patients during the first 6 months following initiation of PD (73.9%). Peritonitis episodes rarely resulted in relapse or the need for permanent hemodialysis and no patient deaths were directly attributable to peritonitis. Antibiotic regimens included cefazolin+tobramycin from the years of 1986 to 2000 and cefazolin+ceftazidime from the years of 2001 to 2011. While antibiotic therapy was successful in 48 episodes (85.7%), the treatment was ineffective in 8 episodes (14.3%). The rate of continuous ambulatory PD (CAPD) peritonitis was statistically higher than that of automated PD (APD) (p=0.025). Conclusion Peritonitis was an important complication of PD therapy and we observed a higher incidence of PD peritonitis in patients with CAPD when compared to APD.

Predictive factors for ciclosporin-associated nephrotoxicity in children with minimal change nephrotic syndrome

Aims To identify the predictive factors for ciclosporin A (CyA)-associated nephrotoxicity (CAN) in children with minimal change nephrotic syndrome (MCNS). Methods The clinical and laboratory findings of 58 children (median age 3.2 years, range 1.1–13.1 years, male:female 48:10) with MCNS who were treated with CyA from 1992 to 2002 were analysed retrospectively. Forty-eight (83%) of them were steroid dependent and 10 (17%) were steroid resistant. The starting dose of CyA was 5 mg/kg per day, and the desired drug level was kept at 100–200 ng/ml. Serial renal biopsies were performed before and after CyA therapy. Results Twenty-two patients (38%) had CAN (group I) and 36 (62%) did not (group II). There were no differences in the age at onset, sex, initial response to steroids, duration of CyA therapy and relapse rates. However, the median CyA trough levels were significantly higher in group I than in group II (218.0±15.2 vs 171.8±6.7 ng/ml, p=0.01). Changes in creatinine clearance were more decreased in group I than in group II (−39.4±8.2 vs 2.7±4.3 ml/min per 1.73 m2, p<0.0001). Multiple logistic regression analysis also revealed the median CyA trough level was an independent risk factor for the development of CAN (OR 1.025, 95% CI 1.007 to 1.044, p=0.007). Conclusions The median CyA trough level was an independent and significant risk factor for the development of CAN in children with MCNS receiving moderate-dose CyA.

Noninfectious Complications of Peritoneal Dialysis in Korean Children: A 26-Year Single-Center Study

Purpose The aim of this study was to investigate noninfectious complications of peritoneal dialysis (PD), including mechanical and metabolic complications, at a single center in Korea. Materials and Methods We analyzed data from 60 PD patients aged ≤18 years (40 boys and 20 girls) during the period between 1986 and 2012. The collected data included gender, age, causes of PD, incidence of noninfectious complications, and treatment for the complications. Results The mean duration of PD therapy was 28.7±42.1 months (range 1-240 months). The most common cause of end-stage renal disease was glomerular disease (43.3%). There were no statistically significant differences between patients with and without mechanical complications regarding gender, age at the start of PD, and total duration of PD. Outflow failure was the most common catheter-related complication (14.3%), followed by leakage (10.0%) and hernia (8.6%). Metabolic complications, such as hyperglycemia and hypokalemia, were observed in three of 16 patients. The frequency of noninfectious complications of PD in our study was comparable with those in previous pediatric studies. PD was switched to hemodialysis (HD) in only three patients. Conclusion Our results indicate that noninfectious complications of PD are common, though they hardly lead to catheter removal or HD in pediatric patients on PD.

Hypokalemic paralysis and rhabdomyolysis in distal renal tubular acidosis

Distal renal tubular acidosis (RTA) is caused by impaired distal acidification and is characterized by the inability to lower urine pH maximally (below 5.5) under the stimulus of systemic acidemia. 1 Characteristic symptoms of distal RTA include polyuria, hypercalciuria, nephrocalcinosis, growth retardation, acidosis, and hypokalemia. 1 The most prominent clinical features of hypokalemia are neuromuscular manifestations, that include muscle weakness and paralysis, as well as an increased incidence of rhabdomyolysis. 2 Rhabdomyolysis can be a life-threatening disorder, with acute renal failure being one of the most serious complications. 3

Influence of cyclosporine A on glomerular growth and the effect of mizoribine and losartan on cyclosporine nephrotoxicity in young rats

The aim of this study was to evaluate the influence of cyclosporine A (CsA) on glomerular growth and the effect of mizoribine (MZR) and losartan (LSAR) on CsA-induced nephropathy in young rats. Six-week-old male Sprague-Dawley rats maintained on a low salt diet were given CsA (15 mg/kg), CsA and LSRT (30 mg/kg/day), CsA and MZR (5 mg/kg), or a combination of CsA, LSRT, and MZR for 4 and 7 weeks (two experiments) and compared with control group (olive oil-treated). Histopathology and glomerular size, inflammatory and fibrotic factors were studied. The score of acute CsA toxicity significantly decreased in the CsA + MZR group compared to the CsA group (p < 0.01). MZR and MZR + LSRT reduced tubulointerstitial fibrosis and TGF-β1 mRNA expression at 7 weeks. Osteopontin (OPN) mRNA expression was decreased at 7 weeks in MZR + LSRT (p < 0.01). Glomerular area decreased CsA group and recovered in MZR (p < 0.01) and MZR + LSRT (p < 0.01) at 7weeks. This study demonstrated that MZR and LSRT had suppressive effects on inflammatory process in chronic CsA nephropathy and led to improvement of tubular damage, tubulointerstitial fibrosis and arteriolopathy by down regulation of OPN and TGF-β1 and glomerular size contraction.

Dense deposit disease in Korean children: a multicenter clinicopathologic study.

The purpose of this study was to investigate the clinical, laboratory, and pathologic characteristics of dense deposit disease (DDD) in Korean children and to determine whether these characteristics differ between Korean and American children with DDD. In 2010, we sent a structured protocol about DDD to pediatric nephrologists throughout Korea. The data collected were compared with previously published data on 14 American children with DDD. Korean children had lower 24-hr urine protein excretion and higher serum albumin levels than American children. The light microscopic findings revealed that a higher percentage of Korean children had membranoproliferative glomerulonephritis patterns (Korean, 77.8%; American, 28.6%, P = 0.036), whereas a higher percentage of American children had crescents (Korean, 0%; American, 78.6%, P < 0.001). The findings from the electron microscopy revealed that Korean children were more likely to have segmental electron dense deposits in the lamina densa of the glomerular basement membrane (Korean, 100%; American, 28.6%, P = 0.002); mesangial deposit was more frequent in American children (Korean, 66.7%; American, 100%, P = 0.047). The histological findings revealed that Korean children with DDD were more likely to show membranoproliferative glomerulonephritis patterns than American children. The degree of proteinuria and hypoalbuminemia was milder in Korean children than American children.