The Protective Role of KANK1 in Podocyte Injury.

Approximately 30% of steroid-resistant nephrotic syndromes are attributed to monogenic disorders that involve 27 genes. Mutations in KANK family members have also been linked to nephrotic syndrome; however, the precise mechanism remains elusive. To investigate this, podocyte-specific Kank1 knockout mice were generated to examine phenotypic changes. In the initial assessment under normal conditions, Kank1 knockout mice showed no significant differences in the urinary albumin-creatinine ratio, blood urea nitrogen, serum creatinine levels, or histological features compared to controls. However, following kidney injury with adriamycin, podocyte-specific Kank1 knockout mice exhibited a significantly higher albumin-creatinine ratio and a significantly greater sclerotic index than control mice. Electron microscopy revealed more extensive foot process effacement in the knockout mice than in control mice. In addition, KANK1-deficient human podocytes showed increased detachment and apoptosis following adriamycin exposure. These findings suggest that KANK1 may play a protective role in mitigating podocyte damage under pathological conditions.

Prognosis of acute myocardial infarction in patients on hemodialysis stratified by Killip classification in the modern interventional era (focus on the prognosis of Killip class 1).

Cardiovascular events and death are more prevalent in hemodialysis (HD) patients than in the general population. However, a detailed prognostic risk stratification of HD patients with acute myocardial infarction (AMI) has not yet been performed in the modern interventional era. We examined 4509 AMI patients (89 AMI/HD and 4420 AMI/non-HD) from the Mie ACS registry and detailed prognostic analyses based on the Killip classification were performed (Cohort A). In addition, prognosis of Killip class1 AMI/HD was compared with those of 313 non-AMI/HD patients from the MIE-CARE HD study using propensity score-matching method (Cohort B). Primary endpoint was all-cause mortality for up to 2 years. All-cause death occurred in 13.0% of AMI/non-HD and 35.8% of AMI/HD during follow-up, and patients with Killip class 1 had lower 30-day and 2-year mortality than those with Killip class ≥ 2 in both AMI/non-HD and AMI/HD. Cox regression analyses identified that Killip class ≥ 2 was the strongest independent prognostic factor of 30-day mortality with a hazard ratio of 7.44 (p < 0.001), whereas both presence of HD and Killip class ≥ 2 were the independent prognostic factors of mortality for up to 2 years. In Cohort B, a propensity score-matching analysis revealed similar all-cause mortality rates between Killip class 1 AMI/HD and non-AMI/HD. In HD patients with Killip class 1 AMI, 30-day mortality was around 6%, and long-term mortality among 30-day survivors after AMI was comparable with the natural course of HD patients in the modern interventional era. Clinical trial registration: URL: https://www.umin.ac.jp/ctr/index-j.htm . UMIN000036020 and UMIN000008128.

Efficacy of xanthine oxidase inhibitor for chronic kidney disease patients with hyperuricemia.

BACKGROUND: Hyperuricemia is a known risk factor for end-stage renal disease. Although xanthine oxidase (XO) inhibitors are expected to protect the kidney function, evidence to this end is insufficient at present. METHODS: This study was a multi-center, open-labeled, randomized study conducted in Mie Prefecture in Japan. Patients were included if they were between 20 and 80 years old and had a serum uric acid (sUA) level ≥ 7.0 mg/dl with or without gout, estimated glomerular filtration rate (eGFR) of 15-60 ml/min/1.73 m2, and urinary protein creatinine ratio (uPCR) of 0.15-3.5 g/gCr. Patients were randomly assigned to a Topiroxostat or Febuxostat group, and the treatment target for the sUA level was < 6.0 mg/dl. The primary outcome was the change in the uPCR after 24 weeks. RESULTS: The change in the median uPCR after 24 weeks was not statistically significant after treatment in the Topiroxostat or Febuxostat group (0.05 g/gCr and - 0.04 g/gCr, respectively). However, the sUA levels decreased significantly in both groups (Topiroxostat group: 8.6 ± 1.1 at baseline to 6.0 ± 1.1 mg/dl at 24 weeks, Febuxostat group: 8.4 ± 1.1 mg/dl at baseline to 5.9 ± 1.3 mg/dl at 24 weeks). No significant change in the eGFR after 24 weeks was noted in either the Topiroxostat or Febuxostat group (- 0.04 ± 4.59 ml/min/1.73 m2 and 0.31 ± 4.70 ml/min/1.73 m2, respectively). CONCLUSIONS: In this study, XO inhibitors did not significantly reduce the uPCR in chronic kidney disease stage 3 and 4 patients with hyperuricemia.

Echocardiographic Assessment of Cardiac Structural and Functional Abnormalities in Patients With End-Stage Renal Disease Receiving Chronic Hemodialysis.

BACKGROUND: The aim of this study was to assess the echocardiographic characteristics of chronic hemodialysis (HD) patients with end-stage renal disease (ESRD) in a multicenter prospective cohort study.Methods and Results:Three hundred and fifteen patients with ESRD (67.9±10.6 years, 47.6% male) on chronic HD for ≥1 year were examined on transthoracic echocardiography, including Doppler-derived aortic valve area (AVA) measurement. Only 11.5% and 3.4% of all patients had normal left ventricular (LV) geometry and normal LV filling pattern, respectively. The majority of patients had aortic and mitral valvular calcification, and approximately 50% of all 315 patients had aortic valve narrowing with AVA <2.0 cm2. Patients were divided into 3 groups according to AVA index tertile: group 1, highest tertile; group 2, middle tertile; and group 3, lowest tertile. Group 3 was older, had a greater cardiothoracic ratio on chest X-ray, higher plasma brain natriuretic peptide and total LV afterload, and lower stroke volume index than the other 2 groups. Age and intact parathyroid hormone (PTH) level were independently associated with low AVA index. CONCLUSIONS: Patients with ESRD on chronic HD have a high prevalence of cardiac structural and functional abnormalities including calcified aortic sclerosis. High age and PTH were associated with aortic valve narrowing in these patients.

Acute kidney injury due to thin basement membrane disease mimicking Deferasirox nephrotoxicity: a case report.

BACKGROUND: Although the renal toxicity of Deferasirox, an oral iron chelator, has been reported to be mild, there have been reports of acute interstitial nephritis or Fanconi syndrome due to this agent. Thin basement membrane disease (TBMD) is a hereditary disease characterized primarily by hematuria, with gross hematuria also observed in about 7% of cases. We herein report a case of TBMD that presented with acute kidney injury and gross hematuria during treatment with Deferasirox. CASE PRESENTATION: The patient was a 63-year-old man who had been diagnosed with myelodysplastic syndrome 6 years ago. He had started taking Deferasirox at 125 mg due to post-transfusion iron overload 6 months ago. Deferasirox was then increased to 1000 mg three months ago. When the serum creatinine level increased, Deferasirox was reduced to 500 mg three weeks before hospitalization. Although the serum creatinine level decreased once, he developed a fever and macroscopic hematuria one week before hospitalization. The serum creatinine level increased again, and Deferasirox was stopped four days before hospitalization. He was admitted for the evaluation of acute kidney injury and gross hematuria. Treatment with temporary hemodialysis was required, and a kidney biopsy was performed on the eighth day of admission. Although there was no major abnormality in the glomeruli, the leakage of red blood cells into the Bowman's space was observed. Erythrocyte cast formation was observed in the tubular lumen, which was associated with acute tubular necrosis. The results of an electron microscopic study were compatible with TBMD. CONCLUSION: Although Deferasirox is known to be nephrotoxic, gross hematuria is relatively rare. When we encounter a case of acute kidney injury with gross hematuria during treatment with Deferasirox, TBMD should be considered as a possible cause of gross hematuria.

Podocyte-specific Crb2 knockout mice develop focal segmental glomerulosclerosis.

Crb2 is a cell polarity-related type I transmembrane protein expressed in the apical membrane of podocytes. Knockdown of crb2 causes glomerular permeability defects in zebrafish, and its complete knockout causes embryonic lethality in mice. There are also reports of Crb2 mutations in patients with steroid-resistant nephrotic syndrome, although the precise mechanism is unclear. The present study demonstrated that podocyte-specific Crb2 knockout mice develop massive albuminuria and microhematuria 2-month after birth and focal segmental glomerulosclerosis and tubulointerstitial fibrosis with hemosiderin-laden macrophages at 6-month of age. Transmission and scanning electron microscopic studies demonstrated injury and foot process effacement of podocytes in 6-month aged podocyte-specific Crb2 knockout mice. The number of glomerular Wt1-positive cells and the expressions of Nphs2, Podxl, and Nphs1 were reduced in podocyte-specific Crb2 knockout mice compared to negative control mice. Human podocytes lacking CRB2 had significantly decreased F-actin positive area and were more susceptible to apoptosis than their wild-type counterparts. Overall, this study's results suggest that the specific deprivation of Crb2 in podocytes induces altered actin cytoskeleton reorganization associated with dysfunction and accelerated apoptosis of podocytes that ultimately cause focal segmental glomerulosclerosis.

Elevated serum levels of bromine do not always indicate pseudohyperchloremia.

BACKGROUND: We encountered a case of bromism that was found to be due to pseudohyperchloremia. Hyperchloremia is known to be able to reveal existing bromism, but the fact that bromine (Br(-)) influences chloride (Cl(-)) in assays that use ion electrode machines is not widely known. METHODS: We assayed samples by an ion electrode method, using four types of machines. Different amounts of Cl(-) or Br(-) were added to each sample. RESULTS: With the addition of Cl(-) to the samples, the assayed Cl(-) concentrations were proportional to the amount of added Cl(-). With the addition of Br(-) to the samples, the assayed Cl(-) concentrations, as measured by all machines, were increased, but the amounts of the increase differed significantly, and were not proportional to the amount of Br(-) added. In particular, in the machine most markedly influenced by additional Br(-), the Cl(-) concentrations increased from 94.9 to 139.6 mEq/l with the addition of 10 mEq/l of Br(-). Conversely, in the least influenced machine, Cl(-) values increased from 95.0 to 103.0 mEq/l with the addition of 10 mEq/l of Br(-). CONCLUSION: The influence on the Cl(-) assay of the addition of Br(-) varied significantly between different ion electrode machines. Clinical nephrologists therefore need to be able to recognize the characteristics of the specific machines used in their hospitals.

How long is strict bed rest necessary after renal biopsy?

BACKGROUND: No consensus exists on the amount of bed rest required after renal biopsy. Moreover, forced prolonged bed rest can be uncomfortable in patients undergoing renal biopsy. OBJECTIVE: To evaluate whether the length of strict bed rest affects the incidence of pain and other complications after renal biopsy. STUDY DESIGN, FACILITY, AND PATIENTS: This single-center retrospective observational study was conducted in 94 consecutive patients undergoing biopsy of a native kidney between November 2005 and December 2006 at Mie University Hospital. The control group was composed of 317 patients who underwent biopsy of a native kidney between January 2001 and October 2005. METHODS: The incidence of biopsy-related complications was compared between two periods of strict bed rest: 2 h of strict bed rest with no abdominal bandage (November 2005 to December 2006) and 7 h of strict bed rest with an abdominal bandage (January 2001 to October 2005). The primary outcome was the incidence of back pain requiring analgesics. The secondary outcomes were: need for transfusion or hemostatic intervention, decrease of >/=10% in hemoglobin (Hb) after biopsy, macroscopic hematuria, infection possibly related to biopsy, need for single or indwelling bladder catheterization, and other biopsy-related complications. RESULTS: The incidence of back pain requiring analgesics decreased with a shorter period of strict bed rest [7.5% versus 21.1%, odds ratio (OR) 0.30, 95% confidence interval (95% CI) 0.12-0.64, p = 0.004]. Even after adjustment for age, sex, perinephric hematoma size, and number of biopsy punctures, the incidence of back pain decreased significantly (OR 0.34, 95% CI 0.14-0.73, p = 0.01). With a shorter period of strict bed rest, there were no significant differences in bleeding complications (need for transfusion or other hemostatic intervention), decrease of >or=10% in Hb or macroscopic hematuria. However, the need for indwelling bladder catheterization decreased significantly (36.2% versus 50.5%, OR 0.55, 95% CI 0.34-0.88, p = 0.013). CONCLUSIONS: Shortening the period of strict bed rest after renal biopsy from 7 h to 2 h decreased the incidence of back pain, but there was no increase in bleeding or other biopsy-related complications. Our findings suggest that a shorter period of strict bed rest can safely reduce discomfort in renal biopsy patients.

Relationship between renal function and serum magnesium concentration in elderly outpatients treated with magnesium oxide.

AIMS: We investigated the relationship between renal function and serum magnesium concentration in elderly patients treated with magnesium oxide (MgO) in an outpatient setting of an urban hospital in Japan. METHODS: In the present study, 44 elderly outpatients (23 patients with constipation treated with daily oral MgO and 21 untreated patients in the control group) who visited Kameyama municipal medical center were enrolled. Variables were age, sex, weight, height, serum magnesium concentration, serum blood urea nitrogen level, serum creatinine level, use of other magnesium-containing supplements and symptoms associated with hypermagnesemia. We calculated the estimated glomerular filtration rate (eGFR) and classified patients based on eGFR category. RESULTS: Compared with the control group, the MgO group showed a significantly higher concentration of serum magnesium (median 2.2 mg/dL [interquartile range 2.1-2.3] vs 2.4 mg/dL [2.2-2.6], P < 0.001). Hypermagnesemia (>2.6 mg/dL) was noted only in the MgO group. However, symptoms associated with hypermagnesemia occurred in patients from both groups, with no significant difference between groups. In the MgO group, significant difference was seen in the median serum magnesium concentration between eGFR categories (P < 0.05). The category G4 (eGFR 15-29 mL/min/1.73 m(2) ) group had the highest serum magnesium concentration in the MgO group (3.0 mg/L [2.9-3.1]). CONCLUSIONS: Elderly patients treated with MgO have higher serum magnesium levels compared with the control group. MgO should be prescribed with caution in patients with low renal function as shown by a GFR category G3b or less (eGFR < 30 mL/min/1.73 m(2) ). Geriatr Gerontol Int 2016; 16: 600-605.