Steroid- and immunosuppressant-based protocol of Henoch-Schönlein purpura nephritis without angiotensin inhibitors in the acute phase.

BACKGROUND: The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggest initially using angiotensin-converting-enzyme inhibitors (ACE-Is) and/or angiotensin receptor blockers (ARBs) to treat Henoch-Schönlein purpura nephritis (HSPN). However, these guidelines might overlook the potential benefits of aggressive therapy. Therefore, we evaluated the efficacy of an HSPN protocol that primarily uses steroids and immunosuppressants, without ACE-Is or ARBs. METHODS: We determine treatment intensity based on International Study of Kidney Diseases in Children (ISKDC) grading. Fifty-one patients were treated with our protocol that primarily uses steroids and immunosuppressants. ACE-Is and ARBs were not used in the acute phase, including before renal biopsy. We evaluated the proteinuria disappearance rate, duration to proteinuria disappearance, and estimated glomerular filtration rate (eGFR) at the time of last observation and compared them to those in previous reports. RESULTS: Proteinuria disappeared in 49 patients (96%) within a median of 5 months. The median eGFR was 116.0 mL/min/1.73 m2 at the time of last observation. Six of 51 patients had acute kidney injury (eGFR<90 mL/min/1.73 m2) before treatment, but all recovered during the observation period (median 52 months). CONCLUSIONS: Our steroid- and immunosuppressant-based protocol without ACE-Is or ARBs in the acute phase of HSPN had almost equivalent efficacy to that in previous studies that used ACE-Is and/or ARBs with steroids and immunosuppressants.

Galactose-deficient IgA1 Is Involved in IgA Deposition in Renal Grafts Biopsied One Hour after Kidney Transplantation.

Objective Asymptomatic renal immunoglobulin A (IgA) deposition occurs in healthy subjects, but its etiologic role in disease is unclear. Galactose-deficient IgA1 (Gd-IgA1) is involved in the pathogenesis of IgA nephropathy. We investigated Gd-IgA1 deposition in transplanted kidneys that were considered healthy showing subclinical latent IgA deposition one hour after transplantation. Methods A total of 723 transplanted kidney specimens biopsied 1 h after kidney transplantation from 2009 to 2016 at Nagoya Red Cross Hospital were examined. A total of 81 cases of IgA deposition were extracted, and 41 were ultimately studied. Double immunofluorescence staining for Gd-IgA1 and IgA was conducted to investigate the role of Gd-IgA1 in subclinical IgA deposition. Results Light microscopy findings for the 41 cases indicated only minor glomerular abnormalities. Immunofluorescence analyses revealed that all cases were positive for IgA. C3, IgG, and IgM positivity rates were 78.0%, 7.3%, and 60.9%, respectively. All 41 cases were positive for Gd-IgA1, which merged with IgA deposition in immunofluorescence double staining. IgA disappeared in 26 of 40 cases (65.0%) 1 year after kidney transplantation. In contrast, IgA redeposition was observed in three cases. Conclusion Gd-IgA1 was demonstrated in all transplanted kidneys, with latent IgA deposition noted in otherwise healthy kidneys. Deposition of Gd-IgA1 might indicate the initial stage of IgA nephropathy; however, additional factors, such as IgG deposition, are required for the ultimate development of IgA nephropathy.

Usefulness of brain natriuretic peptide to distinguish Kawasaki disease from cervical lymphadenitis.

BACKGROUND: Cervical lymphadenitis (CL) cannot be easily distinguished from Kawasaki disease (KD). We therefore explored whether brain natriuretic peptide (BNP) levels are useful in this context. METHODS: We retrospectively analyzed 14 children with CL and 177 children with KD. Patients with KD were divided into three groups according to their clinical symptoms at hospitalization - 97 patients had typical KD, 35 had node-first KD (NFKD), and 45 had KD without lymphadenopathy. We reviewed data on clinical and laboratory parameters, including serum BNP levels, at hospitalization together with factors that might distinguish KD from CL. RESULTS: Patients with CL were older than those with KD. Serum BNP levels were higher in all the KD groups than in the CL group. Multivariate logistic regression analyses indicated that higher BNP levels were associated with NFKD (odds ratio: 1.12, 95% confidence interval: 1.01-1.25). The receiver operating characteristic curve yielded a BNP cutoff of 18.3 pg/mL, with a sensitivity of 0.680, a specificity of 0.857, and an area under the curve of 0.806 (95% confidence interval: 0.665-0.947). CONCLUSIONS: Serum BNP levels can be used to distinguish KD from CL, especially in patients with NFKD.

Insulin-like growth factor-1 level is a poor diagnostic indicator of growth hormone deficiency.

We evaluated the diagnostic accuracy of insulin-like growth factor-1 (IGF-1) for screening growth hormone deficiency (GHD) to determine the usefulness of IGF-1 as a screening test. Among 298 consecutive children who had short stature or decreased height velocity, we measured IGF-1 levels and performed growth hormone (GH) secretion test using clonidine, arginine, and, in cases with different results of the two tests, L-dopa. Patients with congenital abnormalities were excluded. GHD was defined as peak GH ≤ 6.0 ng/mL in the two tests. We identified 60 and 238 patients with and without GHD, respectively. The mean IGF-1 standard deviation (SD) was not significantly different between the GHD and non-GHD groups (p = 0.23). Receiver operating characteristic curve analysis demonstrated the best diagnostic accuracy at an IGF-1 cutoff of - 1.493 SD, with 0.685 sensitivity, 0.417 specificity, 0.25 positive and 0.823 negative predictive values, and 0.517 area under the curve. Correlation analysis revealed that none of the items of patients' characteristics increased the diagnostic power of IGF-1. IGF-1 level had poor diagnostic accuracy as a screening test for GHD. Therefore, IGF-1 should not be used alone for GHD screening. A predictive biomarker for GHD should be developed in the future.

Procalcitonin as a Biomarker of Unresponsiveness to Intravenous Immunoglobulin for Kawasaki Disease.

OBJECTIVE: To investigate the usefulness of procalcitonin (PCT) as predictive factors of intravenous immunoglobulin (IVIG)-resistant Kawasaki disease patients. METHODS: We retrospectively analyzed the laboratory data from 215 children with Kawasaki disease treated with IVIG from 2014 to 2019. We analyzed the clinical and laboratory parameters just before the IVIG including serum levels of PCT with respect to the IVIG response. RESULTS: Eventually, 127 patients were analyzed. The median age was 2.4 years. IVIG was effective in 108 children (responders) and was ineffective in 19 (non-responders). Serum PCT concentration was higher in non-responders than those of responders (P < 0.001). Multivariate logistic regression analyses indicated that higher PCT concentration (odds ratio 1.34, 95% confidence interval 1.10-1.64) were associated with IVIG resistance. Analyses of the receiver operating characteristic curve showed that the cutoff value of PCT 2.18 ng/mL had 46.4% of sensitivity and 93.9% of specificity. Receiver operating characteristic analysis yielded an area under the curve of 0.82 (0.72-0.92) to predict IVIG resistance. CONCLUSIONS: Serum PCT value can be an excellent biomarker for predicting unresponsiveness to IVIG with a good discriminatory ability as well as the existing prediction scores.

Effectiveness and nephrotoxicity of a 2-year medium dose of cyclosporine in pediatric patients with steroid-dependent nephrotic syndrome: determination of the need for follow-up kidney biopsy.

BACKGROUND: High dose of cyclosporine (CyA) for ≥2 years in children with steroid-dependent nephrotic syndrome (SDNS) increases the risk for nephropathy. Considering this, risk can be lowered with lower doses of CyA; we evaluated the effects of a medium dose of CyA, with target serum level, C2, of 450 ng/ml, over a 2-year period of observation, to determine the need for follow-up kidney biopsy. METHODS: We retrospectively evaluated C2 levels in 38 patients (17 males, 5.2 ± 2.9 years old) with SDNS at treatment initiation, at 6, 12 and 18 months during treatment, and at the time of kidney biopsy, 2-year after treatment initiation. Fifteen patients were also treated with mizoribine or mycophenolate mofetil. A number of relapses-per-patient-per-year, relative to SDNS onset and initiation of CyA treatment, were evaluated. Serum levels of total protein, albumin and total cholesterol, blood urea nitrogen level, and the estimated glomerular filtration rate were measured at treatment initiation and at 1- and 2-year post-treatment initiation. RESULTS: Only one very mild case of CyA-associated nephrotoxicity was identified based on biopsy results at 2-year post-treatment initiation. C2 concentrations were maintained at 422.2 ± 133.5 ng/ml and the number of relapses decreased from 3.0 relapses-per-patient-per-year prior to CyA treatment to 0.47 relapses-per-patient-per-year after CyA treatment. No effects of the treatment on the estimated glomerular filtration rate were noted. CONCLUSION: A 2-year treatment with a medium dose of cyclosporine A with or without other immunosuppressive agents is relatively safe with regard to the development of cyclosporine A nephrotoxicity.

Warfarin-induced toxic epidermal necrolysis in combination therapy of Henoch-Schönlein purpura nephritis: a case report.

BACKGROUND: Toxic epidermal necrolysis (TEN) is a rare life-threatening condition almost exclusively attributed to drugs. The main etiologic factors for TEN are sulphonamides, anticonvulsants, and antibiotics; however, there are no published reports of warfarin causing TEN. CASE PRESENTATION: We present the case of a 3-year-old patient who developed TEN while receiving treatment for Henoch-Schönlein purpura nephritis (HSPN). With multiple-drug therapy comprising prednisolone, mizoribine, dipyridamole, and warfarin, it is difficult to detect which drug is the causative agent. While in most cases, diagnosis of the causative drug is based on clinical history without a lymphocyte transformation test (LTT), we performed the test three times and identified the causative drug as warfarin at the late phase. We continued HSPN treatment without warfarin, and results showed good renal function without life-threatening complications. CONCLUSION: To our knowledge, this is the first report about TEN caused by warfarin. Repeated LTTs could be useful for identifying TEN-causative drugs even in the late phase.

Case report: anti-glomerular basement membrane antibody disease with normal renal function.

BACKGROUND: Anti-glomerular basement membrane (GBM) antibody disease is a rare autoimmune disorder characterized by rapidly progressive glomerulonephritis caused by autoantibodies against the α3-chain of type IV collagen in the GBM. CASE PRESENTATION: An 8-year-old girl with hematuria and proteinuria due to anti-GBM nephritis was diagnosed with hematuria and proteinuria during a school urine screening program. Her blood pressure and serum creatinine levels were normal. Her hematuria and proteinuria persisted for several months. Since a spot urine protein to creatinine ratio was around 7 g/g Cre, a percutaneous renal biopsy was performed. Immunofluorescent staining demonstrated a linear pattern for immunoglobulin G along the entire GBM. Chest computed tomography was normal. Anti-GBM antibody assays were reported as slightly raised; thus, the diagnosis was anti-GBM disease with normal renal function. Treatment included plasma exchange, intravenous high-dose methylprednisolone, and cyclophosphamide as a mainstay medication. The treatment was rapidly effective with an immediate decrease in anti-GBM titers and proteinuria. CONCLUSIONS: Cases of anti-GBM disease with normal renal function in children are rare. Treatment in children has not been established; therefore, clinicians need to carefully select an effective treatment because the prognosis is poor.

A case of atypical hemolytic uremic syndrome due to anti-factor H antibody in a patient presenting with a factor XII deficiency identified two novel mutations.

A 9-year-old boy with pallor and macrohematuria showed hemolytic anemia, thrombocytopenia and renal failure. There was no history of diarrhea and the stool culture was negative. A diagnosis of atypical hemolytic uremic syndrome (HUS) was confirmed; however, the cause of the prolonged activated partial thromboplastin time (APTT) was unknown. Plasma exchange and hemodialysis were performed because of progressive hemolytic anemia and renal dysfunction. Fresh frozen plasma was administered frequently to correct the prolonged APTT after hemolysis was controlled and C3 levels had recovered. Factor H (FH) and factor I (IF) levels were normal and we did not detect mutations of FH, IF and membrane cofactor protein. Further investigation revealed the presence of anti-FH antibody in the patient's plasma and a deficiency of coagulation factor XII. Analysis of the patient's coagulation system displayed <3% functional activity of factor XII, whereas levels of other coagulation factors were within the normal range. Two novel mutations (W222G and R447S) were identified upon analysis of the factor XII gene in this patient. Moreover, further investigation revealed that compound heterozygous mutations were present in two of the patient's three siblings, while the third sibling only had a mutation at W222G. The patient was treated for atypical HUS; however, no treatment was required for factor XII deficiency as he did not display a hemorrhagic tendency. We report here a rare case of atypical HUS due to anti-FH antibody presenting with a coagulation factor XII deficiency.