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Autosomal dominant polycystic kidney disease (ADPKD) develops into end-stage kidney disease by 65 years of age in an estimated 45%-70% of patients. Recent trials revealed that tolvaptan inhibits disease progression both in early-stage or late-stage ADPKD ; however, stratified analysis showed a difference of favorable factors correlated with tolvaptan efficacy between early-stage and late-stage ADPKD. Thus, we examined the efficacy of tolvaptan in ADPKD with a wide range of estimated glomerular filtration rates (eGFR). We enrolled 24 patients with eGFR 35.3 (28.0-65.5) ml / min / 1.73m2 and evaluated treatment effect as ΔΔeGFR (ml / min / 1.73m2 / year) or ΔΔtotal kidney volume (TKV) (% / year) that was calculated as post-treatment annual change - pre-treatment annual change. Pre ΔeGFR was significantly low in eGFR responders, defined as ΔΔeGFR > 0 ml / min / 1.73m2 / year. In eGFR responders, pre ΔeGFR, post ΔeGFR, eGFR, TKV, and proteinuria were significantly correlated with ΔΔeGFR. In TKV responders defined as ΔΔTKV > 5 % / year, we identified hypertension history, proteinuria, TKV, and post ΔTKV as significantly correlated factors with ΔΔTKV. In conclusion, pre ΔeGFR may be a predictive factor of therapeutic efficacy on kidney function. Tolvaptan may have greater efficacy in early-stage ADPKD with rapid GFR decline or with well-controlled blood pressure.

Diabetic nephropathy (DN) is the major cause of end-stage renal failure and is associated with increased morbidity and mortality as compared to other causes of renal disease. Albuminuria is often the first clinical indicator of the presence of DN. However, albuminuria or proteinuria is a common symptom in patients with various renal disorders. Therefore, specific biomarkers for the diagnosis of DN are required. A primary hallmark of DN is the progressive damage and death of glomerular podocytes, resulting in the leaking of proteins into the urine. Urinary exosomes released by podocytes are microvesicles containing information of the originated cells. Podocyte-derived signal transduction factors (PDSTFs) are good candidates to assess podocyte injuries. The profile of PDSTFs in urinary exosomes from patients with DN is different from that from patients with minimal change nehrotic syndrome. In addition, PDSTFs molecules in exosomes were derived from primary murine podocytes under high glucose conditions. Among PDSTFs in urinary exosomes, Wilms tumor 1 (WT1) levels reflected damage of diabetic glomeruli in the patients. Urinary exosomal WT1 can predict the decline in eGFR for the following several years. In conclusion, urinary exosomal WT1 is a useful biomarker to improve risk stratification in patients with DN.

Amyloidosis is often overlooked because its clinical manifestations can mimic those of more-common diseases. It is important to get a precise diagnosis as early as possible for the prevention of further organ damages. Amyloidosis is a disorder caused by deposition of insoluble abnormal amyloid. The kidney is a frequent site of amyloid deposition. The amyloid fibrils have a characteristic appearance and generate birefringence under polarized light when stained with the Congo red dye. Classification of amyloidosis is based on the precursor protein that forms the amyloid fibrils and the distribution of amyloid deposits as either systemic or localized. Involvement of amyloid fibrils in kidneys mainly occurs as amyloid light-chain (AL) or amyloid A (AA) amyloidosis. The potassium permanganate method with Congo red staining was once used widely to discriminate AL and AA amyloidoses, but thismethod has a problem of false positive results. We found that extracellular and cytoplasmic glomerular 4’,6-diamidino-2-phenylindole (DAPI)-positive areas were clearly consistent with amyloid deposition in AL amyloidosis. In contrast, the overlapping staining was not seen in AA amyloidosis. Therefore, we propose that DAPI staining readily distinguishes AL renal amyloidosis from AA renal amyloidosis as a simple and reproducible histochemical method.

Pre-pump arterial pressure (PreAP) is monitored to avoid generating excessive negative pressure. National Kidney Foundation K/DOQI clinical practice guidelines for vascular access recommend that PreAP should not fall below-250 mmHg because excessive negative PreAP can lead to a decrease in the delivery of blood flow, inadequate dialysis, and hemolysis. Nonetheless, these recommendations are consistently disregarded in clinical practice and pressure sensors are often removed from the dialysis circuit.Thus far,delivered blood flow has been reported to decrease at values more negative than -150 mmHg of PreAP. These values have been analyzed by an ultrasonic flowmeter and not directly measured. Furthermore, no known group has evaluated whether PreAP-induced hemolysis occurs at a particular threshold. Therefore, the aim of this study was to clarify the importance of PreAP in the prediction of inadequate dialysis and hemolysis. By using different diameter needles, human blood samples from healthy volunteers were circulated in a closed dialysis circuit. The relationship between PreAP and delivered blood flow or PreAP and hemolysis was investigated. We also investigated the optimal value for PreAP using several empirical monitoring methods, such as a pressure pillow. Our investigation indicated that PreAP is a critical factor in the determination of delivered blood flow and hemolysis,both of which occured at pressure values more negative than -150 mmHg. With the exception of direct pressure monitoring, commonly used monitoring methods for PreAP were determined to be ineffective. We propose that the use of a vacuum monitor would permit regular measurement of PreAP.

Circulating ApolipoproteinL1 (ApoL1) is a component of pre-β-high-density lipoprotein (HDL), however little is known about the relationship of ApoL1 with cardiometabolic factors. Considering previous studies reporting the correlation of ApoL1 to triglyceride, we have hypothesized that ApoL1 associates with insulin-related metabolism. The current study examined their associations in 126 non-diabetic subjects and 36 patients with type 2 diabetes (T2DM). Non-diabetic subjects demonstrated triglyceride (standardized coefficients [s.c.] = 0.204, p < 0.05), body mass index (s.c. =0.232, p < 0.05) and HDL cholesterol (s.c. = −0.203, p < 0.05) as independent determinant of ApoL1 levels, and the significant elevation of ApoL1 in metabolic syndrome. Lipoprotein fractionation analysis revealed the predominant distribution of ApoL1 in large HDL fraction, and the significant increase of ApoL1 in large LDL fraction in high ApoL1 samples with insulin resistance. In T2DM, ApoL1 was higher in T2DM with metabolic syndrome, however ApoL1 was lower with β cell dysfunction. Insulin significantly promotes ApoL1 synthesis and secretion in HepG2 cells. In conclusion, circulating ApoL1 may be associated with abnormal HDL metabolism in insulin resistant status. This may suggest a regulation of insulin signal on the ApoL1 level, leading to offer a novel insight to the ApoL1 biology.