Heterozygous missense variant in TRPC6 in a boy with rapidly progressive infantile nephrotic syndrome associated with diffuse mesangial sclerosis.

Transient receptor potential channel C6 encoded by TRPC6 is involved in slit diaphragm formation in podocytes, and abnormalities of the TRPC6 protein cause various glomerular diseases. The first identified pathogenic variant of TRPC6 was found to cause steroid-resistant nephrotic syndrome that typically developed in adulthood and then slowly led to end-stage renal disease, along with a renal pathology of focal segmental glomerulosclerosis. Here, we report a patient with rapidly progressing infantile nephrotic syndrome and a heterozygous missense TRPC6 variant. The patient, a 2-year-old Japanese boy, developed steroid-resistant nephrotic syndrome at age 11 months. His renal function deteriorated rapidly, and peritoneal dialysis was introduced at age 1 year and 6 months. His renal pathology, obtained at age 1 year and 1 month, was consistent with diffuse mesangial sclerosis (DMS). Clinical exome analysis and custom panel analysis for hereditary renal diseases revealed a reported heterozygous missense variant in TRPC6 (NM_004621.5:c.523C > T:p.Arg175Trp). This is the first report of a patient with a TRPC6-related renal disorder associated with DMS.

Impact of acute kidney injury on overall survival in children and young adults undergoing allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Acute kidney injury (AKI) is a complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Increasing severity of AKI is associated with an increased risk of death. However, the impact of AKI in patients with malignant versus nonmalignant disease has not been reported. We investigated the incidence of AKI within the first 100 days after allo-HSCT and the impact of AKI on both 3-year overall survival (OS) and cumulative incidence of death after allo-HSCT in all patients and in patients with/without malignant primary diseases. METHODS: We performed a retrospective analysis of 107 consecutive pediatric and young adult patients who received their first allo-HSCT. AKI was classified into three grades according to the Acute Kidney Injury Network classification system. RESULTS: The cumulative incidences of AKI stages 1-3, 2-3, and 3, at day 100 after allo-HSCT were 34.6% (95% confidence interval [CI], 25.7%-43.6%), 17.8% (95% CI, 11.2%-25.6%), and 3.7% (95% CI, 1.2%-8.6%), respectively. OS was reduced for patients with AKI compared with patients without AKI (60.4% vs. 79.6%, p = .038). The cumulative incidence of death in the AKI group with nonmalignant disease was significantly higher than that in the no-AKI group (44.4% vs. 0%, p = .003). CONCLUSION: AKI after allo-HSCT was not only a frequent event but also related to reduced OS. We recommend that all patients receiving allo-HSCT, especially patients with nonmalignant diseases, be closely monitored for AKI.

Assessment of kidney function using inulin-based and estimated glomerular filtration rates before and after allogeneic hematopoietic stem cell transplantation in pediatric patients.

BACKGROUND: Accurate evaluation of kidney function before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is important for both informed decision making and detection of chronic kidney disease. However, to the best of our knowledge, no report has evaluated the glomerular filtration rate (GFR) in pediatric patients who underwent HSCT using the gold standard GFR measurement, as well as inulin-based GFR (iGFR). METHODS: We assessed iGFR before and after allo-HSCT to evaluate the impact of allo-HSCT on GFR in a prospective cohort study of 17 pediatric patients. We also assessed the accuracy and bias of the values of estimated GFR (eGFR) calculated using serum creatinine (Cr), cystatin C (CysC), beta-2 microglobulin (ß2 MG), 24-h creatinine clearance (24hCcr), and the full chronic kidney disease in children (CKiD) index that combines Cr, CysC, and blood urea nitrogen-based equations with iGFR as a reference to identify the most reliable equation for GFR. RESULTS: There was no significant difference between the values before and after allo-HSCT. CKiD CysC-, 24hCcr-, and full CKiD-based values showed good within 30% (P30) accuracy (80.6%, 79.3%, and 80.6%, respectively), but only 24hCcr and full CKiD had good mean bias (8.5% and 8.9%, respectively) and narrow 95% limits of agreement (-32.2 to 52.7 mL/min/1.73 m2 and -29.3 to 47.4 mL/min/1.73 m2 , respectively) compared with the corresponding iGFR. CONCLUSION: There was no significant impact of allo-HSCT on GFR in our cohort. The most reliable equations for pediatric patients with allo-HSCT were eGFR-24hCcr and eGFR-full CKiD.

Recurrent Abdominal Pain Due to Acute Renal Failure With Loin Pain and Patchy Renal Ischemia After Anaerobic Exercise.

Acute renal failure with severe loin pain and patchy renal ischemia after anaerobic exercise (ALPE) is a rare condition characterized by severe loin pain and patchy renal ischemia following vigorous exercise. Moreover, its diagnosis relies on clinical manifestations. Here, we present the case of a 16-year-old male with recurrent abdominal pain attributed to ALPE. He developed recurrent abdominal pain after he started playing handball, and no definite cause could be identified despite a thorough examination. His symptoms worsened when he resumed handball practice after a one-month interruption. This case underscores the varied presentations of ALPE and the importance of considering it in the differential diagnosis of recurrent abdominal pain, particularly following strenuous exercise. Moreover, caution should be exercised when resuming exercise after periods of detraining, as this may predispose individuals to ALPE. Healthcare providers should be vigilant in recognizing and managing this condition, especially in individuals with recent exercise initiation following detraining.

Unrelated cord blood transplantation using minimal-intensity conditioning in a 1.5-month-old infant with X-linked severe combined immunodeficiency.

BACKGROUND: Severe combined immunodeficiency (SCID) is a heterogenous disorder with profound deficiency of T/B-cell functions. The best SCID therapy requires hematopoietic stem cell transplantation (HSCT) early in life. HSCT with conditioning is necessary to achieve a long-term reconstitution of B-cell functions. However, conditioning may aggravate pre-existing infection and cause transplant-related toxicity, especially in very young infants. Hence, the intensity of conditioning should be reduced to allow the reconstitution of immunity including B cells to the extent that prevents transplant-related toxicity and delayed complications. METHODS: An infant with a family history of X-linked SCID (X-SCID) was diagnosed with X-SCID disorder soon after birth. The infant exhibited cytomegalovirus (CMV) infection despite being strictly isolated. At 1.5 months of age, we performed an unrelated cord blood transplantation (CBT) with a less intensity conditioning regimen: fludarabine (125 mg/m2) + melphalan (80 mg/m2). We evaluated the efficacy of reconstitution by assessing B-cell function and growth and psychomotor development at 5 years and 7 months after CBT. RESULTS: The clinical course after CBT was uneventful after CBT. The CMV infection was fully controlled by ganciclovir or foscavir therapy, which was discontinued at day 55 after CBT. Furthermore, immunoglobulin (Ig) replacement therapy was also discontinued at 6 months after CBT. A sufficient proportion of CD27+ memory B cells was developed, which was essential for an effective vaccination and prevention of infections. While the B-cell chimerism became recipient-dominant, the Ig replacement therapy was substituted by very successful post-vaccine immunity acquisition after CBT. The analysis of the general developmental parameters showed that chemotherapy did not cause any delay in growth and psychomotor development. CONCLUSIONS: The CBT therapy with this conditioning regimen was well tolerated and induced an effective reconstitution of B-cell functions in an X-SCID infant under the 3 months of age.

Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema Following Posterior Reversible Encephalopathy Syndrome in a Child: A Case Report.

Angioedema is a rare but potentially lethal side effect of angiotensin-converting enzyme inhibitors (ACEIs). Most ACEI-induced angioedema (ACEI-AE) cases have been reported in adults, with few reports of cases in children. Posterior reversible encephalopathy syndrome (PRES) is a neurological disorder that presents with acute onset of symptoms, including headache, vomiting, visual disturbances, and seizures. We report the case of a patient who developed ACEI-AE after developing PRES during the treatment of steroid-resistant nephrotic syndrome. ACEI-AE is very rare, especially in children, but can be life-threatening if swelling of the tongue or the throat blocks the airway. Whenever ACEIs are used, even in children, clinicians should be aware of the possibility of the occurrence of ACEI-AE, particularly when accompanied by dry cough. Moreover, bradykinin may be associated with PRES onset in patients with ACEI-AE and may be a risk factor for PRES.

Proteinuria from first-morning urine in a child due to brace treatment for adolescent idiopathic scoliosis.

A first-morning urine test for screening urinary protein is important for distinguishing whether asymptomatic proteinuria, which is a common finding in school-aged children, is caused due to kidney disease or not. We report the case of a 12-year-old Japanese girl who was referred to our pediatric department for asymptomatic proteinuria detected during a school urinary screening. Proteinuria was found only on the first-morning urinalysis and not on the routine urinalysis. The patient had been diagnosed with adolescent idiopathic scoliosis and treated with a nighttime brace. As excess protein was not detected on urinalysis of the first-morning urine sample that was collected after a night without the brace, proteinuria due to the brace treatment for scoliosis was diagnosed. The present case revealed that brace treatment can cause proteinuria. Even if a first-morning urine is positive for protein, an unexpected cause can trigger asymptomatic proteinuria in a growing child.

Impact of infliximab administration before plasma exchange therapy on patients with Kawasaki disease.

Plasma exchange is a therapeutic option in refractory Kawasaki disease (KD). However, the effects of other immunosuppressive treatments on plasma exchange therapy have not been studied. We investigated the effect of infliximab on plasma exchange in KD as well as on the outcome in patients with KD. We studied 16 patients with intravenous immunoglobulin-resistant KD who finally underwent plasma exchange. The patients were divided into two groups: patients who received infliximab before plasma exchange (infliximab group) and patients who did not (non-infliximab group). The infliximab group showed a lesser median number of required total plasma exchange sessions (P = .002) and higher change and reduction rates in C-reactive protein before and after the first plasma exchange (both P = .027) than that of the non-infliximab group. Infliximab administered before plasma exchange reduced the number of total plasma exchange sessions and improved the plasma exchange efficacy.