Renal and cardiac biopsy findings in an adolescent patient with the 3243A>G mitochondrial DNA mutation: Favorable renal prognosis post renal transplantation from the mother.

We investigated the pathogenesis of a perihilar variant of focal segmental glomerulosclerosis detected by kidney biopsy in a 16-year-old male. The disease was refractory to steroid therapy, and at the second kidney biopsy, abnormal mitochondrial proliferation was newly observed in the podocytes. The patient also developed late-onset hearing loss and had a family history of diabetes, and genetic testing confirmed the mitochondrial DNA mutation 3243A>G (48%). Eight months after hemodialysis was started, encephalopathy occurred presumably due to rapid dehydration. After changing dialysis into continuous ambulatory peritoneal dialysis, encephalopathy was resolved, but the patient developed myocardial hypertrophy, probably because of the myocardial overreaction to congestion. A myocardial biopsy showed mitochondrial proliferation in the myocardium. After renal transplantation from his mother with a heteroplasmy of 4%, the cardiomyopathy improved, and the renal function has remained stable for 4 years. We speculated that the abnormal mitochondrial morphology in the kidney and heart may be characteristic of mitochondrial genetic disease, and renal transplantation from the mother with a low heteroplasmy was considered desirable for mitochondrial nephropathy with poor prognosis.

Efficacy and safety of first-line biological DMARDs in rheumatoid arthritis patients with chronic kidney disease.

OBJECTIVE: To evaluate the efficacy and safety of first-line biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) with chronic kidney disease (CKD), including those undergoing haemodialysis (HD). METHODS: This retrospective cohort study included 425 patients with RA prescribed their first bDMARDs at two hospitals from 2004 to 2021. Patients were categorised by kidney function and bDMARD modality (TNFα inhibitors (TNFαis), interleukin-6 inhibitors (IL-6is), cytotoxic T-lymphocyte antigen-4 immunoglobulin (CTLA4-Ig)). The primary outcome was the 36-month drug retention rate, with secondary outcomes including changes in Disease Activity Score 28 (DAS28)-C reactive protein (CRP)/erythrocyte sedimentation rate (ESR), prednisolone dosage and reasons for discontinuation. RESULTS: The 36-month drug retention rates by estimated glomerular filtration rate (eGFR) (≥60, 30-60, <30 mL/min/1.73 m2) were as follows: all bDMARDs (45.2%, 32.0%, 41.4%), TNFαis (45.3%, 28.2%, 34.0%), IL-6is (47.4%, 66.7%, 71.4%) and CTLA-4Ig (50.0%, 31.3%, 33.3%). Even in groups with lower kidney function, the drug retention rate of bDMARDs was generally maintained. However, the retention rate of TNFαis was significantly lower in patients with eGFR <30 mL/min/1.73 m2. IL-6is showed the highest retention rate and the lowest discontinuation rate due to ineffectiveness in this group (HR 0.11, 95% CI 0.02 to 0.85, p=0.03). All bDMARDs improved DAS28-CRP/ESR and reduced prednisolone dosage across all groups. CONCLUSION: bDMARDs demonstrated effective and safe profiles in patients with RA with CKD, even among patients on HD. In particular, IL-6is had a significantly higher drug retention rate in patients with an eGFR of <30 mL/min/1.73 m2 and fewer discontinuations due to ineffectiveness. IL-6is were more efficacious as monotherapy compared with the other bDMARDs.

A Case of C3 Nephritis With a Rare Variant of the CFHR5 Gene.

C3 nephropathy is a renal disease caused by the aberrant activation of the alternative complement pathway. The long-term renal prognosis of C3 nephropathy is generally poor, and elucidation of its pathogenesis is clinically important. Genetic abnormalities within complement genes, encompassing autoantibodies targeting complement components and complement factor H-related proteins (CFHRs), can lead to abnormal complement activation. CFHR5 is one of the best-known responsible genes for C3 nephritis. Moreover, the renal prognosis can vary depending on the specific type of genetic mutation. Here, we report the case of a young woman with C3 nephritis and a heterozygous rare variant, P453S, in CFHR5. The P453S variant, characterized by amino acid substitutions with a low allele frequency, was located in the region essential for CFHR5 protein function, and multiple in silico analyses were done suggesting the pathological significance of P453S. The renal function of our patient remains stable. The P453S variant might contribute to the suppression of the CFHR5 protein's function, resulting in gradual complement progression and a favorable renal prognosis.

A Rare Case of Drug Reaction with Eosinophilia and Systemic Symptoms Syndrome Leading to Hemodialysis and Multiple Infections: A Case Report and Literature Review.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe drug eruption that causes multiple organ damage. The renal impairment in these patients usually improves with immunosuppressants, but subsequent infections often develop. We herein report a rare case of DRESS syndrome leading to hemodialysis and multiple infections with Pneumocystis pneumonia, cytomegalovirus and Aspergillus despite the administration of low-dose prednisolone. We also present a literature review of cases requiring dialysis after DRESS syndrome. In patients with chronic kidney disease, it is important to be alert for not only the development of DRESS syndrome but also subsequent infections.

Efficacy of SGLT2 inhibitors in IgA nephropathy associated with alcoholic liver cirrhosis accompanied by nephrotic syndrome: a case report.

We present a 51-year-old male patient with a history of Child-Pugh Grade B alcoholic liver cirrhosis (ALC) who developed renal impairment (serum creatinine of 2.00 mg/dL) and nephrotic syndrome (a urinary protein level of 4.35 g/gCr). The patient was diagnosed with immunoglobulin A nephropathy (IgAN) associated with ALC based on findings from comprehensive evaluations, including markedly elevated serum IgA levels (883.7 mg/dL), a kidney biopsy revealing significant IgA deposition in the para-mesangial area, and a liver diagnosis showing long-standing advanced ALC. Our treatment approach involved initiating dapagliflozin therapy, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, alongside strict alcohol abstinence. Remarkably, the patient demonstrated a dramatic reduction in proteinuria within one week of dapagliflozin administration. No hypoglycemic events were observed. This case adds valuable clinical insights into the potential therapeutic role of SGLT2 inhibitors in IgAN associated with ALC. Specifically, in cases where conventional steroid therapies may be contraindicated due to coexisting comorbidities such as diabetes or obesity, dapagliflozin emerges as a potentially efficacious alternative. Further investigations are warranted to validate these preliminary observations.

Molecular structures and mechanisms of DNA break processing in mouse meiosis.

Exonucleolytic resection, critical to repair double-strand breaks (DSBs) by recombination, is not well understood, particularly in mammalian meiosis. Here, we define structures of resected DSBs in mouse spermatocytes genome-wide at nucleotide resolution. Resection tracts averaged 1100 nt, but with substantial fine-scale heterogeneity at individual hot spots. Surprisingly, EXO1 is not the major 5' → 3' exonuclease, but the DSB-responsive kinase ATM proved a key regulator of both initiation and extension of resection. In wild type, apparent intermolecular recombination intermediates clustered near to but offset from DSB positions, consistent with joint molecules with incompletely invaded 3' ends. Finally, we provide evidence for PRDM9-dependent chromatin remodeling leading to increased accessibility at recombination sites. Our findings give insight into the mechanisms of DSB processing and repair in meiotic chromatin.

Analysis of possible structures of inducible skin-associated lymphoid tissue in lupus erythematosus profundus.

Lupus erythematosus profundus (LEP) is a variant of lupus erythematosus, involving the deep dermis and subcutaneous fat. LEP is characterized by the presence of lymphoid follicles (LF) and germinal centers (GC). However, it remains unknown whether these lymphoid structures correspond to the lymphoid tissues such as cutaneous tertiary lymphoid organs (TLO). Previously, we identified dynamically orchestrated cellular elements in murine contact dermatitis that resembled lymphoid structures, which we termed inducible skin-associated lymphoid tissues (iSALT). We subsequently reported structures analogous to iSALT in human secondary syphilis, suggesting that iSALT can also exist in humans. Here, we studied ectopic lymphoid tissues in the lesions of LEP by immunohistochemistry and compared their characteristics with those of TLO. We demonstrated that LF of LEP were composed of B-cell follicles intermingled with CXCL13-expressing cells, distinct aggregations of T cells, and some blood vessels expressing peripheral node addressin. These findings indicate that LF of LEP can be considered as a type of iSALT.