Harboyan syndrome: novel SLC4A11 mutation, clinical manifestations, and outcome of corneal transplantation.

Harboyan syndrome or corneal dystrophy and progressive deafness (MIM #217400) is characterized by congenital hereditary endothelial dystrophy (CHED) and progressive, sensorineural hearing loss. Mutations in SLC4A11 are responsible for this rare genetic syndrome. Eight patients from seven unrelated families affected with Harboyan Syndrome with mean follow-up of 12.0 ± 0.9 years were thoroughly investigated for the ocular, hearing, and kidney function abnormalities and the outcome of penetrating keratoplasty (PK). Mutation analysis of SLC4A11 was performed. All patients presented with bilateral cloudy corneas since birth. Sensorineural hearing loss was detected in all patients. Seven patients (11 eyes) underwent PK with the median age at surgery of 10.1 years (7.1-22.9). The overall corneal graft survival rate after primary PK was 72.7% (8/11 eyes). The mean graft survival time was 94.6 months (95% CI 83.1-126.0). All patients had unremarkable kidney function. The c.2264G>A (p.Arg755Gln) mutation in SCL4A11 was detected in most patients (87.5%). All unrelated Karen tribe patients had p.Arg755Gln mutation, suggestive of founder effect. We found the allele frequency of this variant in the Karen population to be 0.01. The c.2263C>T (p.Arg755Trp) mutation was found in one patient with mild phenotype and the novel truncating protein mutation c.2127delG (p.Gly710fsx*25) in SCL4A11 was identified in two Thai sisters. Visual outcome and graft survival after PK were satisfactory. Our study shows that all studied patients with SLC4A11 mutations had CHED and sensorineural hearing loss, and SLC4A11 mutations were not related to the onset and severity of hearing loss or outcome of keratoplasty.

Vitamin C deficiency and impact of vitamin C administration among pediatric patients with advanced chronic kidney disease.

BACKGROUND: Vitamin C deficiency is common in chronic kidney disease (CKD) due to losses through dialysis and dietary intake below requirement. We investigated prevalence of vitamin C deficiency and impact of vitamin C treatment in deficient/insufficient patients. METHODS: A prospective cohort study in patients aged 1-18 years with CKD stages 4 and 5D collected demographic data including underlying disease, treatment, and anthropometric assessment. Vitamin C intake was assessed using 24-h dietary recall. Hemoglobin, iron status, serum vitamin C, and serum oxalate were measured at baseline and after treatment. Vitamin C (250 mg/day) was given orally for 3 months to deficient/insufficient patients. RESULTS: Nineteen patients (mean age 12.00 ± 4.1 years) showed prevalence of 10.6% vitamin C insufficiency and 78.9% deficiency. There were no associations between vitamin C level and daily vitamin C intake (p = 0.64) or nutritional status (p = 0.87). Median serum vitamin C was 1.51 (0.30-1.90) mg/L. In 16 patients receiving treatment, median serum vitamin C increased from 1.30 (0.23-1.78) to 3.22 (1.77-5.96) mg/L (p = 0.008) without increasing serum oxalate (79.92 (56.6-106.84) vs. 80.47 (56.88-102.95) µmol/L, p = 0.82). However, 62.5% failed to achieve normal vitamin C levels. Ordinal regression analysis revealed patients with non-oligoanuric CKD were less likely to achieve normal vitamin C levels (ß = - 3.41, p = 0.03). CONCLUSION: We describe high prevalence of vitamin C insufficiency/deficiency among pediatric CKD patients. Vitamin C levels could not be solely predicted by nutritional status or daily intake. The treatment regimen raised serum vitamin C without increasing serum oxalate; however, it was largely insufficient to normalize levels, particularly in non-oligoanuric CKD. Graphical abstract .

Prevalence and associated factors of renal dysfunction and proteinuria in cyanotic congenital heart disease.

BACKGROUND: Cyanotic nephropathy (CN), seen in 30-50% of patients with congenital cyanotic heart disease (CCHD), affects both tubular and glomerular function, resulting in proteinuria and azotemia. Microalbuminuria is an early marker for glomerular damage and an independent predictor of progressive renal disease. METHODS: A cross-sectional study was conducted. A total of 116 patients aged 1 month to 15 years with CCHD at Chiang Mai University Hospital between 2015 and 2016 were assessed and 94 patients were enrolled. To determine the prevalence and associated factors of significant albuminuria in CCHD patients, baseline characteristics, oxygen saturation, surgery, hemoglobin (Hb), hematocrit (Hct), spot urine albumin, urine protein, and creatinine were obtained. Binary logistic-regression modeling was used to identify associated factors. RESULTS: Prevalence of CN in children with CCHD was 58.51% and 92.55% according to albuminuria and proteinuria staging respectively. Prevalence of significant proteinuria, significant albuminuria, and decreased GFR was 88.30%, 41.49% and 31.91% respectively. Participants with significant albuminuria had fewer previous surgeries (p = 0.05), a longer waiting time for surgery (p = 0.02), enalapril usage (p = 0.04), pulmonary hypertension (p = 0.03), higher Hct z-score (p = 0.03) and lower platelet count (p = 0.001) compared with those without significant albuminuria. Using multivariate logistic regression analysis, waiting duration for surgery (p = 0.04), Hct >40% (p = 0.02), and platelet count <290,000/mm3 (p = 0.04) were predictive of microalbuminuria. CONCLUSIONS: Cyanotic nephropathy can be detected in the first decade of life with the presentation of microalbuminuria. High Hct level and low platelet count were identified as a predictor of microalbuminuria, whereas early cardiac surgery decreased the risk of developing significant albuminuria.

Clinical Course, Outcomes and Complications of Thai Pediatric Pure Type versus Mixed Type Lupus Membranous Nephritis.

Background: Due to the relative infrequency of lupus membranous nephritis (LMN) compared to other types of lupus nephritis (LN) in pediatric patients, the current literature on pediatric LMN is limited. The knowledge regarding clinical manifestations, outcomes and infectious complications are mainly based on studies in the adult population. Similar to disease expression in SLE, the renal manifestations of LMN are affected by environmental factors and vary among racial and ethnic groups. Objective: To describing clinical features, common infectious complications, and outcomes of pediatric-onset LMN in Thailand and the correlation between pure and mixed types of LMN classified by renal pathology. Material and Method: This was a retrospective analysis of 40 patients with LMN as seen in the Pediatric Nephrology Clinic, Maharaj Nakorn Chiang Mai from January, 2003 to December, 2012. Patients were categorized into pure and mixed types of LMN the comparisons of the clinical course, results of treatment and infectious complications between the two types had been analyzed and recorded data for 2 years. Results: Kidney biopsy was performed. Of the 40 patients with LMN, 50% were diagnosed as mixed-type LMN. The clinical symptoms presented including rash, hypertension, edema, serositis and arthritis were found at 57.7%, 45%, 40%, 25% and 25% respectively. All of the patients were treated with an immunosuppressive drug such as: Cyclophosphamide, Azathioprine, Cyclosporine or Mycophenolate mofetil, together with systemic steroids. During the two years follow up, every patient had normal GFR. Twenty nine patients (72.5%) had renal remission in proteinuria with complete remission in 7 patients (17.5%) and partial remission in 22 patients (55%). An average time from the onset to remission was 12 months. GFR and proteinuria were not significant difference between the two groups after treatment. The infections found in patients who received cyclophosphamide include herpes infection, salmonellosis, lung abscess, nocardiosis, giardia intestinalis and cerebral cysticercosis. Furthermore, steroid side effect was avascular necrosis of the hip joint. Conclusion: The mixed-type LMN patients had a higher blood pressure, higher BUN and positive LE cell than those of the pure-type LMN patients. Hypertension at initial presentation can be a predictor of proliferative lesion in renal pathology. However, a proliferative lesion accompanied with LMN does not affect renal outcomes. With similar renal outcomes, the immunosuppressive with low adverse effects may be considered as a preferable treatment.

Successful treatment of neonatal pulmonary thrombosis in congenital nephrotic syndrome.

A 21-year-old adult patient with Tetralogy of Fallot presented acutely unwell with a 3-month history of general malaise following dental treatment. Following initial complete repair, he subsequently underwent two right ventricular outflow tract reconstructions with conduits. On admission, transthoracic echocardiography and peripheral blood cultures were suggestive of streptococcal endocarditis. Sequential computed tomography pulmonary angiography demonstrated peripheral emboli with progressive central pulmonary artery filling defects suggestive of thrombi and potential vegetations (Fig 1a and b). Urgent surgery was performed for uncontrolled sepsis and increasing hypoxia. Peri-operative transesophageal echocardiogram confirmed previous findings (Fig 1c; Supplementary Video 1). Having resected the conduit, we performed a peripheral pulmonary embolectomy and resected an abundance of the infected material from the pulmonary arterial tree under low-flow hypothermia; we then proceeded with a jugular venous valved conduit (Contegra®, Medtronic Inc, Minneapolis, Minnesota, United States of America) replacement and tricuspid valve annuloplasty. He made a slow but steady recovery and was discharged home in good health

Pulse cyclophosphamide induction treatment in Thai children with diffuse proliferative lupus nephritis.

AIM: To report the effectiveness of pulse cyclophosphamide induction therapy and to identify predictors for unresponsiveness to treatment in Thai children. METHODS: Children with biopsy-proven diffuse proliferative lupus nephritis admitted to Chiang Mai University hospital between 2001 and 2006 were retrospectively studied. Patients received a test dose of 750 mg/m(2) at the first month followed by six cycles of monthly cyclophosphamide (IVCY) at a dose of 1 g/m(2) (maximum 1 g) as induction therapy. Responsiveness to treatment, defined as urinary protein to creatinine ratio of less than 0.3 with normalization of C3 level and clinical remission, was assessed at the end of the induction period. Gender, age at onset, duration of disease before treatment, hypertension, clinical nephrotic syndrome, amount of proteinuria, serum creatinine, creatinine clearance, serum C3 level and crescentic formation were compared between responsive and nonresponsive groups. Maintenance therapy with quarterly pulse IVCY or Azathioprine or Mycophenolate mofetil was given for 18-24 months after remission. RESULTS: Twenty nine patients with a mean age of 10.3 ± 2.6 years were studied. Hypertension, microscopic haematuria and nephrotic-range proteinuria were seen in 66%, 86% and 60% of the patients, respectively. Forty-one per cent of biopsies showed cellular or fibrocellular crescents. Twenty patients (69%) achieved remission at the end of induction therapy. There were no significant differences in all parameters studied between responsive and nonresponsive groups. The relapse rate after maintenance therapy was 58.8%. CONCLUSION: Our results show that pulse cyclophosphamide is an effective regimen for induction therapy in children with diffuse proliferative glomerulonephritis. No definite predictor for unresponsiveness was detected in this study.

Psychosocial functioning of children with systemic lupus erythematosus.

AIMS: Systemic lupus erythematosus (SLE) is a chronic illness in children. Involvement of multiple systems; the chronicity, as well as the treatment, has had great impact on children and their families. The objective of this study was to assess emotional and behavioural problems in childhood lupus during disease remission. METHODS: Children with SLE and healthy controls, aged 8-15 years, were studied. Disease remission was confirmed by using the SLE Disease Activity Index (SLEDAI). The Children's Depression Inventory (CDI) and Multidimensional Anxiety Scale for Children (MASC) were rated by the children themselves. The Child Behaviour Checklist was completed by their parents. RESULTS: The sample included 40 children with SLE and 40 controls. Their mean age was 12.9 ± 2.1 and 12.1 ± 1.8 years in the SLE and control groups, respectively. The average duration of the disease was 2.6 years. The SLEDAI in the SLE group ranged from 0-1, indicating inactive disease. The mean CDI scores were 8.9 and 10.9 in lupus children and controls, respectively. The mean MASC score was 44.7 in children with SLE and 48.4 in controls. The internalizing, externalizing and total behavioural scores were not significantly different in both groups (9.0 vs. 10.6; 6.6 vs. 8.1; 27.3 vs. 32.5). Only the social competence score was lower in children with SLE (P= 0.03). CONCLUSIONS: SLE is a multi-system involvement disease with wide ranging effects on children's physical and psychosocial functioning. However, children with SLE, during inactive disease, were not found to be at increased risk of psychosocial dysfunctions.

Comparison of Clinical Manifestations, Laboratory, Neuroimaging Findings, and Outcomes in Children With Posterior Reversible Encephalopathy Syndrome (PRES) in Children With and Without Renal Disease.

BACKGROUND: To demonstrate and compare the clinical manifestations, laboratory findings, and neuroimaging findings of posterior reversible encephalopathy syndrome (PRES) in children with and without underlying renal disease. METHODS: The study included 23 children with a diagnosis of PRES from January 2009 to March 2019. All data, including clinical manifestations, laboratory findings, underlying medical illness, and neuroimaging results, were obtained. RESULTS: Sixteen had underlying renal disease. The median age of PRES onset was 10.3 years in children with renal disease and 9.8 years in children without renal disease. Higher blood pressure at the baseline, on admission, and at the onset of PRES was found in the renal disease group more than in the nonrenal disease group (P < 0.05). Seizures were likely seen in the renal disease group compared with the nonrenal disease group (P = 0.03). Generalized tonic-clonic seizures were the most common seizure type in both groups. An initial CT scan revealed vasogenic edema in 75% of the renal group and 85.7% of the nonrenal group. During a long-term follow-up, all children recovered without significant neurological deficits or subsequent epilepsy. CONCLUSIONS: Hypertension and higher baseline blood pressure are more common in children with renal disease who develop PRES compared with nonrenal disease. Seizures are more common in the renal disease group. A computed tomographic (CT) scan can help with PRES diagnosis when magnetic resonance imaging is not available. All children with PRES recovered without significant neurological deficits or subsequent epilepsy.

Interventions for preventing and treating kidney disease in Henoch-Schönlein Purpura (HSP).

BACKGROUND: To determine the benefits and harms of therapies used to prevent or treat kidney disease in Henoch-Schönlein Purpura (HSP). OBJECTIVES: To evaluate the benefits and harms of different agents (used singularly or in combination) compared with placebo or no treatment or another agent for the prevention or treatment of kidney disease in patients with HSP. SEARCH STRATEGY: Randomised controlled trials (RCTs) and quasi-RCTs were identified from the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE using optimally sensitive search strategies combined with search terms for HSP. SELECTION CRITERIA: RCTs comparing any intervention used to prevent or treat kidney disease in HSP compared with placebo, no treatment or other agents were included. DATA COLLECTION AND ANALYSIS: Three authors independently assessed trial quality and extracted data from each study. Statistical analyses were performed using the random effects model and the results were expressed as risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). MAIN RESULTS: Ten studies (1230 children) were identified. There was no significant difference in the risk of persistent kidney disease at six months (3 studies, 379 children: RR 0.51, 95% CI 0.24 to 1.11) and 12 months (3 studies, 498 children: RR 1.02, 95% CI 0.40 to 2.62) in children given prednisone for 14 to 28 days at presentation of HSP compared with placebo or supportive treatment. In children with severe kidney disease, there was no significant difference in the risk of persistent kidney disease with cyclophosphamide compared with supportive treatment (1 study, 56 children: RR 1.07, 95% CI 0.65 to 1.78) and with cyclosporin compared with methylprednisolone (1 study, 19 children: RR 0.39, 95% CI 0.14 to 1.06). AUTHORS' CONCLUSIONS: Data from RCTs for any intervention used in improve kidney outcomes in children with HSP are very sparse except for short-term prednisone. There was no evidence of benefit of prednisone in preventing serious long-term kidney disease in HSP.

Methylprednisolone treatment in children with nephrotic primary focal segmental glomerulosclerosis.

OBJECTIVE: To examine the effectiveness of pulse methylprednisolone in children with nephrotic primary focal segmental glomerulosclerosis. MATERIAL AND METHOD: Medical records of children, who were treated with a pulse methylprednisolone regimen for nephrotic syndrome resulting from primary focal segmental glomerulosclerosis between 1987 and 2005, were retrospectively reviewed. The age, gender, urine protein, serum creatinine, and glomerular filtration rate at the onset of nephrotic syndrome were recorded. Urine protein, serum creatinine, glomerular filtration rate, and percentile of height before and after methylprednisolone treatment were compared. RESULTS: There were six patients (4 male, 2 female) in the present report. The mean age at onset was 9.5 +/- 2.2 years. Hypertension was noted in four patients and mild renal insufficiency in three. All patients had nephrotic-ranged proteinuria at onset and they were initially treated with prednisolone. Two were steroid-dependent and four were steroid-resistant. All of the steroid resistant cases were also resistant to oral cyclophosphamide. After methylprednisolone treatment, remission of proteinuria was noted in five patients (83%) (2 complete, 3 partial). Mean duration to remission was 20.8 weeks. There were no significant changes in serum creatinine (p = 0.43), GFR (p = 0.78) and percentile of height before and after treatment. No hypertension or cardiac arrhythmia was detected during methylprednisolone administration. The follow-up period after completion of the methylprednisolone regimen was 19.5 +/- 15.2 months (range 4-36 months). The clinical course of five patients with remission was characterized by sustained remission in three patients. Two patients relapsed at 2 and 8 months after treatment. CONCLUSION: Methylprednisolone was effective and safe in treating nephrotic children with primary focal segmental glomerulosclerosis. There was a high incidence of relapse shortly after the cessation of treatment. However, a larger number of patients and longer period of follow-up are needed to confirm this conclusion.

Transient hyperkalemia and hypoaldosteronism in a patient with acute glomerulonephritis.

The authors describe a 7-year-old boy with acute glomerulonephritis, who developed acute renal failure in the early course of his disease. While the renal function and other clinical manifestations gradually improved, hyperkalemia occurred unexpectedly, and returned to normal level spontaneously after a short period of symptomatic treatment. With the result of a low transtubular potassium gradient (TTKG) level, it was concluded that hypoaldosteronism was the major cause of hyperkalemia in this patient.

Infection in children with lupus nephritis receiving pulse and oral cyclophosphamide therapy.

Infection is the major complication of cyclophosphamide therapy in patients with lupus nephritis. The objectives of this study were to report and compare the rate of infection between children with lupus nephritis who had received intravenous pulse cyclophosphamide (IVCY) and those who had received oral cyclophosphamide (OCY) and to determine the risk factors for infection during treatment with cyclophosphamide in these groups. Records of nine patients who had received IVCY from the beginning [pure intravenous cyclophosphamide (PIVCY) group], 11 patients who had received prior oral cyclophosphamide and later switched to IVCY [combined intravenous cyclophosphamide (CIVCY) group] and 41 patients who had received OCY were reviewed. Infection occurred in 21 of 61 patients (34%). In the PIVCY group, four episodes of infection occurred in three of nine patients (33%). In the CIVCY group, six episodes of infection occurred in four of 11 patients (36%). In the OCY group, 18 episodes of infection occurred in 14 of 41 patients (34%). The rate of infection between these groups was not different (P=0.99). None of the following parameters were risk factors for infection: cumulative dose of cyclophosphamide, leukopenia and neutropenia. On the contrary, white blood cell (WBC) count and polymorphonuclear cell (PMN) count were significantly less in the no-infection group (P=<0.001, P<0.001, respectively), with odds ratios for leukopenia (WBCs <4,000 mm(3)) and neutropenia (PMNs <1,500 mm(3)) between the infection and the no-infection group equal to 0.18 (95%CI 0.05-0.63) and 0 (95%CI 0-0.19), respectively. Most of the patients who had infection received prednisolone at a dosage of more than 0.5 mg/kg per day (67% of the PIVCY group, 50% of the CIVCY group and 83% of the OCY group). Fatal infections occurred in two patients who had concomitant active systemic lupus erythematosus (SLE). Although lymphopenia (lymphocyte count <1,500/mm(3)) was not the risk factor for infection, it was observed that six of seven patients with herpes zoster had lymphopenia. Herpes zoster seemed to occur more frequently in the OCY group (15%) than in the whole IVCY group (5%), but there was no statistical difference (P=0.41). We conclude that the rate of infection in the IVCY and OCY group was not different. Infection is likely to occur in patients receiving a concomitant high dose of prednisolone. The occurrence of fatal infection in patients with active disease should be noted. No single risk factor was detected in this study.

Steroid-resistant nephrotic syndrome associated with Kimura's disease.

Kimura's disease is a chronic inflammatory disease characterized by tumor-like lesions in the soft tissue and lymph nodes of head and neck area or parotid gland. It has a high frequency of an association with nephrotic syndrome. Reported cases of nephrotic syndrome and Kimura's disease were mostly from adult patients with only 5 children mentioned. This study reports the case of a 15-year-old-boy who manifested with steroid-resistant nephrotic syndrome for 4 years. Pathological examination of the kidney revealed mild mesangial proliferation. Subsequently, he developed a soft-tissue mass in the parotid gland area. Histopathological investigation of the mass revealed eosinophilic infiltration together with plasma cells and mast cells which is a main characteristic of Kimura's disease. The patient, however, continued to have nephrotic-range proteinuria after removing the subcutaneous mass.

A girl with Takayasu arteritis associated with possible systemic lupus erythematosus.

Takayasu arteritis is an inflammatory disease that affects the aorta and its main branches. Its etiology is obscure. Its association with systemic lupus erythematosus has been reported in the English literature in about 20 cases worldwide, and a relationship with a positive tuberculin test, either with or without tuberculosis, has also been mentioned. We report a pediatric patient who presented with renovascular hypertension secondary to Takayasu arteritis associated with a strongly positive tuberculin test and who subsequently developed possible systemic lupus erythematosus 8 months later.

Cytomegalovirus-associated manifestations involving the digestive tract in children with human immunodeficiency virus infection.

OBJECTIVE: To study the clinical manifestations of gastrointestinal cytomegalovirus disease in children with human immunodeficiency virus infection. METHODS: Review of clinical records of eight human immunodeficiency virus-infected children and histopathologically confirmed gastrointestinal cytomegalovirus disease from 1995 to 2001. RESULTS: Six of the eight children were younger than 1 year. The most common clinical presentations were fever and chronic diarrhea. Lower gastrointestinal hemorrhage and bowel perforation were noted in four and three patients, respectively. The colon was the most commonly affected site, followed by the small bowel and esophagus. The diagnosis was established by histopathology, obtained during endoscopy and surgery. Mucosal edema, erythema, and ulcer comprised the most common endoscopic findings. Two patients with fever, chronic diarrhea, and lower gastrointestinal bleeding developed remission after being treated with a 14-day course of ganciclovir. CONCLUSION: Gastrointestinal cytomegalovirus disease can result in serious life-threatening complications, such as bowel perforation and massive gastrointestinal bleeding. Patients with chronic diarrhea and fever of unidentified cause might benefit from gastrointestinal endoscopy for early diagnosis and treatment. Although ganciclovir does not eradicate the infection and relapses are frequent, this treatment can prevent complications and reduce morbidity.