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BackgroundHeterozygous PAX2 mutations cause renal coloboma syndrome (RCS) [OMIM no. 120330]. RCS is a renal syndromic disease encompassing retinal coloboma and sensorineural hearing loss. Recently, a causative role for PAX2 was reported in adult-onset nephrotic syndrome secondary to focal segmental glomerulosclerosis (FSGS). However, the prevalence of PAX2 mutations among large cohort of children with steroid-resistant nephrotic syndrome (SRNS) and FSGS has not been systematically studied.MethodsWe employed whole-exome sequencing (WES) to identify the percentage of SRNS cases explained by monogenic mutations in known genes of SRNS/FSGS. As PAX2 mutations are not an established cause of childhood FSGS, we evaluated a cohort of 215 unrelated families with SRNS, in whom no underlying genetic etiology had been previously established.ResultsUsing WES, we identified 3 novel causative heterozygous PAX2 mutations in 3 out of the 215 unrelated index cases studied (1.3%). All three cases were detected in individuals from families with more than one affected and compatible with an autosomal dominant mode of inheritance (3/57 familial cases studied (5.2%)). The clinical diagnosis in three out of four pediatric index patients was done during routine medical evaluation.ConclusionsOur findings demonstrate high frequency of PAX2 mutations in familial form of SRNS (5.2%) and further expand the phenotypic spectrum of PAX2 heterozygous mutations to include autosomal dominant childhood-onset FSGS. These results highlight the importance of including PAX2 in the list of genes known to cause FSGS in children.

In a trial involving patients with recurrent kidney stones who received once-daily 12.5-mg, 25-mg, or 50-mg doses of hydrochlorothiazide or placebo, the incidence of stone recurrence was similar in all groups.

Background Pembrolizumab is an anti- Programmed Death 1 (PD-1) antibody approved in melanoma, non-small cell lung cancer and investigated in malignant pleural mesothelioma. The most frequent immunotherapy related autoimmune reactions include dermatitis, pneumonitis, colitis, hypophysitis, uveitis, hypothyreodism, hepatitis and interstitial nephritis. Case presentation We describe a 62-year old patient diagnosed with malignant pleural mesothelioma who experienced ten days after the second dose of third line therapy with pembrolizumab sudden onset of generalized edema including legs and eyelids and weight gain of 15 kg resulting from nephrotic syndrome and acute renal failure. Pembrolizumab was discontinued and prednisone, diuretics and angiotensin II receptor blocker were initiated with full recovery of symptoms and renal function. Pembrolizumab-associated minimal change disease (MCD) was confirmed by electron microscopy in the renal biopsy. Conclusion We are the first to describe pembrolizumab-related minimal change disease (MCD). Physicians should be aware of this side effect in patients presenting with edema and weight gain and initiate prompt renal function testing, serum albumin and urinalysis followed by steroid treatment if pembrolizumab-related MCD is suspected.

Background Nephrolithiasis is a global healthcare problem with a current lifetime risk of 18.8% in men and 9.4% in women. Given the high cost of medical treatments and surgical interventions as well as the morbidity related to symptomatic stone disease, medical prophylaxis for stone recurrence is an attractive approach. Thiazide diuretics have been the cornerstone of pharmacologic metaphylaxis for more than 40 years. However, evidence for benefits and harms of thiazides in the prevention of calcium containing kidney stones in general remains unclear. In addition, the efficacy of the currently employed low dose thiazide regimens to prevent stone recurrence is not known. Methods The NOSTONE trial is an investigator-initiated 3-year prospective, multicenter, double-blind, placebo-controlled trial to assess the efficacy of standard and low dose hydrochlorothiazide treatment in the recurrence prevention of calcium containing kidney stones. We plan to include 416 adult (≥ 18 years) patients with recurrent (≥ 2 stone episodes in the last 10 years) calcium containing kidney stones (containing ≥50% of calcium oxalate, calcium phosphate or a mixture of both). Patients will be randomly allocated to 50 mg or 25 mg or 12.5 mg hydrochlorothiazide or placebo. The primary outcome will be incidence of stone recurrence (a composite of symptomatic or radiologic recurrence). Secondary outcomes will be individual components of the composite primary outcome, safety and tolerability of hydrochlorothiazide treatment, changes in urinary biochemistry elicited by hydrochlorothiazide treatment and impact of baseline disease severity, biochemical abnormalities and stone composition on treatment response. Discussion The NOSTONE study will provide long-sought information on the efficacy of hydrochlorothiazide in the recurrence prevention of calcium containing kidney stones. Strengths of the study include the randomized, double-blind and placebo-controlled design, the large amount of patients studied, the employment of high sensitivity and high specificity imaging and the exclusive public funding support. Trial registration ClinicalTrials.gov, NCT03057431 . Registered on February 20 2017.

Rhodococcus equi is an animal pathogen that sometimes causes opportunistic infections in immunocompromised patients. Speck et al . present the case of a 62-year-old male renal transplant recipient who presented with fever, hemoptysis and left-sided pleuritic chest pain. After numerous investigations, a diagnosis of R. equi infection with bacteremic pleuropneumonia and pseudotumor was made. This Case Study describes the diagnosis and management of R. equi infection, which has a very varied clinical presentation in humans. Background A 62-year-old male kidney transplant recipient was admitted to hospital with a 14-day history of fever, hemoptysis and left-sided pleuritic chest pain. He had suffered malaise, weight loss, night sweats and exertional dyspnea over the previous 3 months. Imaging studies of the patient's chest revealed a noncavitated mass measuring 5 × 8 cm in the anterior segment of the left upper lobe of the lung and a left-sided pleural effusion with septa, and bacterial cultures revealed the presence of Rhodococcus equi . Investigations Physical examination, laboratory tests, chest X-ray, CT scan of the chest, bronchoscopy, and bacterial culture of blood, sputum, bronchoalveolar lavage fluid and pleural fluid. Diagnosis R. equi infection with bacteremic pleuropneumonia and pseudotumor. A secondary myopathy occurred 6 months after diagnosis of the infection as a result of a drug interaction between clarithromycin and simvastatin. Management Long-term combination antibiotic therapy (ciprofloxacin plus vancomycin or clarithromycin), resection of the inflammatory pseudotumor, and reduction of immunosuppressive therapy. Following the diagnosis of myopathy, simvastatin was discontinued.