A Case of Rapidly Progressive Diabetic Nephropathy Induced by Osimertinib

The number of patients with diabetic nephropathy is increasing worldwide and it is important to understand the underlying pathological mechanisms of the disease. In early stage diabetic nephropathy, the hyperglycemic environment leads to vascular endothelial cell damage, resulting in overexpression of vascular endothelial growth factor (VEGF) in podocytes and renal pathology of glomerular hypertrophy, glomerular basement membrane thickening, and mesangial hyperplasia. In diabetic nephropathy, renal thrombotic microangiopathy (TMA) develops and the nephropathy progressively worsens in some cases of severe glomerular podocyte damage. Further, receptor tyrosine kinase inhibitors (RTKIs) may suppress VEGF secretion via VEGF receptor-2 tyrosine kinase inhibition in podocytes, which results in renal TMA and rapid deterioration of diabetic nephropathy. Osimertinib, a third-generation irreversible epidermal growth factor receptor (EGFR)-TKI, is approved as a first-line treatment agent for metastatic or locally advanced EGFR mutation-positive non-small cell lung cancer. We encountered a case of a patient with diabetic nephropathy with lung adenocarcinoma treated with osimertinib, whose condition deteriorated from early nephropathy to end-stage renal disease in approximately 4 months. The patient had early diabetic nephropathy, but the use of a RTKI suppressed VEGF expression in podocytes, resulting in the induction of renal TMA and the development of rapidly progressive diabetic nephropathy

シンセイジ ニ タイスル ケイビテキ ジゾク ヨウアツ コキュウ ホウ ノ コウカ ト モンダイ テン

当院新生児集中治療室において経鼻的持続陽圧呼吸法を65例に施行し,その有効性と問題点について疾患別に検討した.出生後早期の呼吸障害である呼吸窮迫症候群では全例無効であったが,新生児一過性多呼吸では79%で有効であった.低出生体重児の慢性肺疾患では,抜管後の呼吸障害に85%で有効であった.無呼吸発作には,呼吸中枢の未熟性によるものには95%で有効であったが,薬剤の副作用による無呼吸に対しては無効であった.経鼻的持続陽圧呼吸法の合併症として,鼻部潰瘍および腹部膨満を3例に認めた.ただ,これらの合併症は,使用時間の短縮で減らすことが可能であると考えられた. Key Words: 新生児,経鼻的持続陽圧呼吸法,無呼吸発作We evaluated the effects and problems of nasal continuouspositive airway pressure (nasal CPAP) in 65 patientsadmitted to our neonatal intensive care unit. In neonateswith early onset respiratory problems after birth, nasalCPAP was effective for 79 % in transient tachypnea. However,no effect was observed in respiratory distress syndrome.Nasal CPAP was also effective for 85 % in post-extubationchronic lung disease and 95 % in apnea ofprematurity. Ulcers around the nose and abdominal distensionas adverse effects were observed in several neonates,however these risks may be reduced by shorting durationof nasal CPAP

シンセイジ ニ タイスル ケイヒテキ チュウシン ジョウミャク (PCV) カテーテル ノ シヨウ ニツイテ : ソノ リテン ト ガッペイショウ

3年間に当院周産期センター新生児部門に入院し,経皮的中心静脈(PCV)カテーテルを使用した新生児は69例であった。これらの症例を対象とし,カテーテルの挿入理由,抜去理由,維持日数,合併症などについて後方視的に検討した。カテーテルの挿入理由は,超低出生体重児の輸液管理目的が最も多く,抜去理由は輸液が不要となった症例が最も多かった。カテーテルの平均維持日数は17.7日であった。カテーテルの留置中の合併症としては敗血症が4例(5.8%)であったが,カテーテル敗血症と診断したのは1例(1.4%)のみであった。その他に胸水貯留と横隔膜挙上の症例を計2例経験した。経皮的中心静脈カテーテルは,長期間にわたって留置が可能であり,合併症が少ないことから,新生児の輸液管理に非常に有用であると考えられた。We used percutaneous central venous catheters (PCV catheters) for 69 neonates, who entered our neonatal intensive care unit for recent 3 years. We retrospectively researched the reasons of insertion and removal of PCV catheters, and complications of the catheters. The catheters were inserted mainly for the maintenance of fluid administration of extremely low birth weight infants, and were removed mainly for the end of fluid administration. The catheters were maintained for 17.7 days on the average. The sepsis occurred in 4 infants (5.8%) during indwelling of PCV catheters, however, only one infant (1.4%) was diagnosed as the catheter-related sepsis. Expect for the sepsis, two infants complicated retention of pleural fluid or elevation of diaphragm. Our results disclosed that PCV catheter caused be use for the long-term indwelling of catheter for fluid administration, and had rare frequency of complications. We conclude that PCV catheter is very useful for the fluid administration of neonates

Mutation Type and Intracranial Aneurysm Formation in Autosomal Dominant Polycystic Kidney Disease

Background Screening for intracranial aneurysms (IAs) in patients with risk factors of IA is recommended. However, genetic risk factors of IA in patients with autosomal dominant polycystic kidney disease (ADPKD) remain unclear, and genotype–phenotype relationships in IAs in patients with ADPKD have not been clarified. Therefore, we aimed to clarify the associations between germline mutations and IA formation in patients with ADPKD. Methods A total of 135 patients with ADPKD who were evaluated for ADPKD mutations were examined for IA formation in this single‐center observational study. Results The incidence of de novo IA formation was 1.3% per patient‐year. Age at IA diagnosis was younger in patients with frameshift (median, 36 years; P=0.003) and splicing mutations (median, 43 years; P=0.046) than in patients with substitutions (median, 63 years). Multivariable analyses showed that IA was associated with female sex (odds ratio [OR], 3.32 [95% CI, 1.10–10.01]; P=0.03), a family history of IA or subarachnoid hemorrhage (OR, 3.05 [95% CI, 1.07–8.71]; P=0.04), estimated glomerular filtration rate (OR, 0.69 [95% CI, 0.54–0.87]; P=0.002), and splicing mutations (OR, 9.30 [95% CI, 1.71–50.44]; P=0.01). Splicing mutations showed a significant association with IA formation even in subcohorts with minimal risk factors for IA, such as age <50 years (OR, 19.52 [95% CI, 3.22–118.51]; P=0.001), nonhypertension (OR, 49.28 [95% CI, 3.60–673.98]; P=0.004), and nonsmoking behavior (OR, 27.79 [95% CI, 3.49–221.21]; P=0.002). Conversely, substitutions showed significant associations with IA formation in subcohorts such as age ≥50 years (OR, 8.66; 95% CI, 1.43–52.51; P=0.02) and chronic kidney disease stages 4 and 5 (OR, 10.70 [95% CI, 1.05–108.75]; P=0.045). Conclusions Genetic analyses in patients with ADPKD could contribute to IA screening and could be useful for evaluating the prognosis, including complications. IA screening should be recommended for patients with ADPKD who have splicing and frameshift mutations and for older patients or patients with advanced ADPKD who have substitutions

Time series changes in pseudo-R2 values regarding maximum glomerular diameter and the Oxford MEST-C score in patients with IgA nephropathy: A long-term follow-up study.

There is no effectual pathological factor to predict the long-term renal prognosis of IgA nephropathy. Glomerular hypertrophy plays a crucial role in kidney disease outcomes in both experimental models and humans. This study aimed to 1) confirm the long-term prognostic significance of a maximal glomerular diameter (Max GD) ≥ 242.3 μm, 2) test a renal prognosis prediction model adding Max GD ≥ 242.3 μm to the Oxford classification (MEST-C), and 3) examine the time series changes in the long-term renal prognosis of patients with IgA nephropathy. The study included 43 patients diagnosed with IgA nephropathy from 1993 to 1998 at Kameda General Hospital. Renal prognosis with the endpoint of a 50% reduction in estimated glomerular filtration rate (eGFR) or the development of end-stage renal disease requiring dialysis was examined using logistic regression analysis, Cox regression analysis, and the Kaplan-Meier method. Pathological evaluation was performed using MEST-C and Max GD, and the validity of the prediction model was evaluated. Patients with Max GD ≥ 242.3 μm had significantly poor renal prognosis with multivariate Cox analysis (P = 0.0293). The results of the Kaplan-Meier analysis showed that kidney survival rates in the high-Max GD group were significantly lower than those in the low-Max GD group (log rank, P = 0.0043), which was confirmed in propensity score-matched models (log rank, P = 0.0426). Adding Max GD ≥ 242.3 μm to MEST-C improved diagnostic power of the renal prognosis prediction model by renal pathology tissue examination (R2: 3.3 to 14.5%, AICc: 71.8 to 68.0, C statistic: 0.657 to 0.772). We confirm that glomerular hypertrophy is useful as a long-term renal prognostic factor

Visceral to subcutaneous fat ratio as an indicator of a ≥30% eGFR decline in chronic kidney disease.

Whether the visceral-to-subcutaneous fat ratio (V/S ratio) is associated with renal prognosis in patients with chronic kidney disease (CKD) remains unclear. Furthermore, little is known about the effect of sex and the absolute amount of visceral fat accumulation such as visceral fat area (VFA) ≥100 cm2 on the V/S ratio in relation to renal prognosis. In this study, 200 patients with CKD were evaluated for renal prognosis. Survival analyses and logistic regression analyses were conducted, generating time-series pseudo-R2 values. The mean and percent change of the pseudo-R2 values from the 6th year to the 10th year (6Y-10Y Mean and 6Y-10Y Change, respectively) were calculated for determining the cut-off points for the medium-term renal prognosis. Multivariate Cox regression analysis revealed that the V/S ratio was significantly associated with renal outcomes and that the VFA category (VFA ≥ 100 cm2) had significant interactions with the V/S ratio regarding renal prognosis. The hazard ratio (HR) of the V/S ratio was higher in the sub-cohort of VFA < 100 cm2 than in the sub-cohort of VFA ≥ 100 cm2 (HR: 6.42 vs. 1.00). Regarding sex differences, a strong association was noted between the V/S ratio and renal prognosis in women but not in men (HR: 2.40 vs. 1.10). On the other hand, 6Y-10Y Mean of the pseudo-R2 values indicated differences in the cut-off points of the V/S ratio between men and women (V/S ratio: 0.75 vs. 0.5). Our findings indicate that it may be clinically meaningful to consider the differences in sex and the amount of VFA ≥100 cm2 for the V/S ratio in relation to renal outcomes in patients with CKD. The 6Y-10Y Mean of the pseudo-R2 values contributed to determining the cut-off points of the V/S ratio according to the sex difference

Maximum Glomerular Diameter and Oxford MEST-C Score in IgA Nephropathy: The Significance of Time-Series Changes in Pseudo-R2 Values in Relation to Renal Outcomes

The progression of immunoglobulin A nephropathy (IgAN) is currently assessed using the Oxford MEST-C score, which uses five indicators (mesangial and endocapillary hypercellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy, and the presence of crescents) but has not yet included any risk factors related to glomerular size. Therefore, we tested whether adding another indicator, maximal glomerular diameter (Max GD), would improve the prognostic ability of this scoring system. The data of 101 adult patients diagnosed with IgAN between March 2002 and September 2004 were reviewed. We used McFadden&rsquo;s pseudo-R2 and the corrected Akaike information criterion to assess model fit and the concordance (C)-statistic to assess discriminatory ability. A 10 &mu;m increase in Max GD was significantly associated with a composite outcome (&ge;50% decline in the estimated glomerular filtration rate or end-stage renal disease). The receiver operating characteristic analysis determined the cut-off for high vs. low Max GD at 245.9 &mu;m, and adding high Max GD to the MEST-C score significantly improved the model&rsquo;s discrimination of renal outcomes at 5 and &ge;10 years. Thus, including the Max GD in the Oxford classification of IgAN might increase its robustness and provide a more comprehensive prognostic system for clinical settings