Dabigatran-induced anticoagulant-related nephropathy with undiagnosed IgA nephropathy in a patient with normal baseline renal function.

Occasionally, over-anticoagulation with warfarin induces acute kidney injury (AKI) characterized by glomerular hemorrhage with tubular obstruction by red blood cell casts, which is widely acknowledged as warfarin-related nephropathy. Owing to extensive use of direct oral anticoagulants, similar AKI cases have been reported among patients treated with dabigatran. Dabigatran is primarily excreted by the kidneys; thus, renal impairment is one of the risk factors for dabigatran-induced bleeding complications. Nevertheless, risk factors for dabigatran-induced anticoagulant-related nephropathy (ARN) remain partially clarified. Here, we report a histologically established case of dabigatran-induced ARN with undiagnosed IgA nephropathy in a patient with normal baseline renal function. In addition, we summarize previously published cases of biopsy-proven, dabigatran-related ARN. A 67-year-old female with normal preexisting renal function developed macrohematuria and AKI. She had been treated with dabigatran for deep vein thrombosis. A renal biopsy diagnosed ARN with inactive IgA nephropathy. After dabigatran withdrawal, her macrohematuria and renal function improved. This report demonstrates that ARN could occur in patients with normal baseline renal function. Our case and prior reports suggest that IgA nephropathy could be a risk factor for dabigatran-induced ARN.

Renin-angiotensin System Blockade Therapy for Early Renal Involvement in MYH9-related Disease with an E1841K Mutation.

MYH9-related disease is a rare genetic disorder characterized by macrothrombocytopenia, with frequent proteinuric nephropathy, hearing loss, and cataract. Although proteinuric nephropathy usually progresses to renal failure, there is no established treatment for the nephropathy. We herein describe the case of a 19-year-old man carrying an E1841K MYH9 mutation, who developed persistent proteinuria. The patient was diagnosed with early-stage MYH9-related nephropathy based on the histological examination of a kidney biopsy specimen. The patient was treated with enalapril, which significantly reduced the proteinuria with no decline in his renal function. The early administration of renin-angiotensin system blockade therapy may have beneficial effects on MYH9-related nephropathy in patients with E1841K mutations. We also briefly summarize previously published cases of MYH9-related nephropathy treated with renin-angiotensin system (RAS) blockade therapy.

Fiber type-specific afferent nerve activity induced by transient contractions of rat bladder smooth muscle in pathological states.

Bladder smooth muscle shows spontaneous phasic contractions, which undergo a variety of abnormal changes depending on pathological conditions. How abnormal contractions affect the activity of bladder afferent nerves remains to be fully tested. In this study, we examined the relationship between transient increases in bladder pressure, representing transient contraction of bladder smooth muscle, and spiking patterns of bladder afferent fibers of the L6 dorsal root, in rat pathological models. All recordings were performed at a bladder pressure of approximately 10 cmH2O by maintaining the degree of bladder filling. In the cyclophosphamide-induced model, both Aδ and C fibers showed increased sensitivity to transient bladder pressure increases. In the prostaglandin E2-induced model, Aδ fibers, but not C fibers, specifically showed overexcitation that was time-locked with transient bladder pressure increases. These fiber type-specific changes in nerve spike patterns may underlie the symptoms of urinary bladder diseases.

Pregnancy Is a Risk Factor for Secondary Focal Segmental Glomerulosclerosis in Women with a History of Very Low Birth Weight.

Low birth weight (LBW) has been known to increase the susceptibility to renal injury in adulthood. A 26-year-old woman developed proteinuria in early pregnancy; she had been born with very LBW. The clinical course was progressive, and an emergency Caesarean section was performed at 36 weeks due to acute kidney injury. A renal biopsy provided a diagnosis of post-adaptive focal segmental glomerulosclerosis. Increased demand for glomerular filtration during early pregnancy appeared to have initiated the renal injury. This report highlights the fact that pregnancy might be a risk factor for renal injury in women born with LBW.

Modulation of afferent nerve activity by prostaglandin E2 upon urinary bladder distension in rats.

NEW FINDINGS: What is the central question of this study? It has been widely assumed that C fibres innervating the bladder are mainly excited in overactive bladder syndrome. However, it remains unclear whether Aδ fibres are also activated in pathological conditions. What is the main finding and its importance? We found that a certain population of Aδ fibres, which become active specifically at a bladder pressure of more than 15 cmH2 O in normal conditions, showed increased excitability in conditions of prostaglandin E2 -induced overactive bladder. This result suggests that a certain population of Aδ fibres, together with C fibres, triggers pathophysiological activity. In overactive bladder syndrome, afferent C fibres innervating the bladder show an increased activity level. However, it remains unclear whether all C fibres are highly activated and whether Aδ fibres, the other type of bladder afferent fibre, are also involved in pathological conditions. To address these questions, we analysed the relationship between bladder pressure and single-unit firing patterns of afferent nerves in the left L6 dorsal roots in living rats. The recorded fibres were classified as Aδ fibres or C fibres based on the response to 0.3 µm tetrodotoxin. Certain populations of both Aδ fibres and C fibres were activated at bladder pressures below 15 cmH2 O (classified as low-threshold fibres), indicating their potential contribution to detection of normal bladder filling. Intravesical administration of prostaglandin E2 (PGE2 ) induced hyperexcitation in approximately half of such C fibres, whereas the activity patterns of low-threshold Aδ fibres were unchanged. All fibres, regardless of type, which were almost silent in control conditions (classified as high-threshold fibres), were activated by application of PGE2 . Notably, the firing patterns of Aδ fibres, rather than C fibres, were highly time locked to PGE2 -induced micro-oscillation of bladder pressure. These modulatory effects of PGE2 on Aδ fibres and C fibres might trigger pathophysiological activity together in overactive bladder syndrome.