A Case of Self-Limiting Crescentic Immunoglobulin A Glomerulonephritis Associated with Sternoclavicular Arthritis

Immunoglobulin (Ig) A glomerulonephritis (GN) is a heterogeneous disease affected by various factors. Genetic and other factors “hit” DNA, causing IgA malformation and ultimately glomerular injury. We describe a rare case of crescentic IgA GN with sternoclavicular (SC) arthritis in a 75-year-old woman. Despite active IgA GN with cellular crescents, the patient achieved remission of IgA GN without glucocorticoid therapy after remission of SC arthritis was achieved. Considering the patient’s clinical course, this case suggested a relationship between IgA GN and SC arthritis

Urinary Level of Liver-Type Fatty Acid Binding Protein Reflects the Degree of Tubulointerstitial Damage in Polycystic Kidney Disease

Background/Aims: Polycystic kidney disease (PKD) is a common, progressive, and heritable type of kidney disease. Although certain imaging modalities are useful for the diagnosis and staging of PKD, they cannot adequately monitor the severity of interstitial inflammation and fibrosis. Therefore, the present study evaluated the urinary level of liver-type fatty acid binding protein (L-FABP) as a marker of interstitial inflammation and fibrosis in PKD. Methods: Male PCK/CrljCrl-Pkhd1pck/Crl (PCK) rats (n = 34) were used as an animal model of the PKD. Age-and sex-matched Sprague–Dawley rats (SD) (n = 34) were used as controls. Urine samples were obtained from the rats at 8, 12, 16, 20, and 24 weeks of age, and the sera and kidney tissues were obtained at 8, 16, 20, and 24 weeks of age. Results: All PCK rats developed cysts, and the degrees of tubular epithelial cell proliferation and interstitial inflammation increased linearly with age in these model rats relative to the controls. Interstitial fibrosis tended to increase in the PCK rats from 8 to 20 weeks of age, and revealed a peak level at 20 weeks. The urinary L-FABP levels increased linearly with age in the PCK rats, and the levels at 12, 16, 20, and 24 weeks were significantly higher than those in the controls. The urinary levels of L-FABP in the PCK rats correlated significantly with the severity of tubulointerstitial damage; specifically, we observed a significant correlation of the urinary levels at 16 weeks of age with the total kidney volume at 20 weeks. In contrast, both PCK and SD rats exhibited similar serum levels of L-FABP. Conclusion: Urinary L-FABP reflects the progression of tubulointerstitial damage, and therefore, may be a useful marker for monitoring the progression of PKD

Hope in Adult Patients with Chronic Disease: Qualitative Study.

To identify the sources of hope for patients with chronic disease, a semi - structured interview was conducted with patients middle-aged and older, whose disease types and levels of activities of daily living limitations varied. Six patience - three with chronic kidney disease, one with rheumatoid arthritis, one with spinal cord injury, and another with lumbar spinal canal stenosis - were interviewed by a psychologist and an internist. It was determined that their sources greatly differed depending on individual circumstances, such as types and severity of disease, sources of joy and happiness, family structure, employment status, relationship with friends, etc. However, it also showed a stylization of hope dependent on individual experience; in other words, there was a tendency for patients to redefine their source of hope by setting attainable goals to match their limitations, or acknowledging what they have achieved and finding hope in maintaining their current state. We have determined that the sources of hope are comprised of two categories: ［foundation and process of finding hope］ and ［specific goals and sources］. The former consists of: ［stylization dependent on experience］, ［method and will］, ［use of external information］, ［intrinsic foundation］, and ［extrinsic foundation］. The latter consists of: ［health］, ［source of joy and happiness］, ［family］, and ［social connections］

Development of Risk Prediction Equations for Incident Chronic Kidney Disease

IMPORTANCE Early identification of individuals at elevated risk of developing chronic kidney disease (CKD) could improve clinical care through enhanced surveillance and better management of underlying health conditions.OBJECTIVE To develop assessment tools to identify individuals at increased risk of CKD, defined by reduced estimated glomerular filtration rate (eGFR).DESIGN, SETTING, AND PARTICIPANTS Individual-level data analysis of 34 multinational cohorts from the CKD Prognosis Consortium including 5 222 711 individuals from 28 countries. Data were collected from April 1970 through January 2017. A 2-stage analysis was performed, with each study first analyzed individually and summarized overall using a weighted average. Because clinical variables were often differentially available by diabetes status, models were developed separately for participants with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external cohorts (n = 2 253 540).EXPOSURES Demographic and clinical factors.MAIN OUTCOMES AND MEASURES Incident eGFR of less than 60 mL/min/1.73 m(2).RESULTS Among 4 441 084 participants without diabetes (mean age, 54 years, 38% women), 660 856 incident cases (14.9%) of reduced eGFR occurred during a mean follow-up of 4.2 years. Of 781 627 participants with diabetes (mean age, 62 years, 13% women), 313 646 incident cases (40%) occurred during a mean follow-up of 3.9 years. Equations for the 5-year risk of reduced eGFR included age, sex, race/ethnicity, eGFR, history of cardiovascular disease, ever smoker, hypertension, body mass index, and albuminuria concentration. For participants with diabetes, the models also included diabetes medications, hemoglobin A(1c), and the interaction between the 2. The risk equations had a median C statistic for the 5-year predicted probability of 0.845 (interquartile range [IQR], 0.789-0.890) in the cohorts without diabetes and 0.801 (IQR, 0.750-0.819) in the cohorts with diabetes. Calibration analysis showed that 9 of 13 study populations (69%) had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 of 18 (89%) had a slope of observed to predicted risk between 0.80 and 1.25.CONCLUSIONS AND RELEVANCE Equations for predicting risk of incident chronic kidney disease developed from more than 5 million individuals from 34 multinational cohorts demonstrated high discrimination and variable calibration in diverse populations. Further study is needed to determine whether use of these equations to identify individuals at risk of developing chronic kidney disease will improve clinical care and patient outcomes.</p

The Japanese Clinical Practice Guideline for acute kidney injury 2016

Acute kidney injury (AKI) is a syndrome which has a broad range of etiologic factors depending on different clinical settings. Because AKI has significant impacts on prognosis in any clinical settings, early detection and intervention are necessary to improve the outcomes of AKI patients. This clinical guideline for AKI was developed by a multidisciplinary approach with nephrology, intensive care medicine, blood purification, and pediatrics. Of note, clinical practice for AKI management which was widely performed in Japan was also evaluated with comprehensive literature search

Nationwide multicentre kidney biopsy study of Japanese patients with type 2 diabetes

金沢大学医薬保健研究域医学系Background. The clinical and pathologic manifestations of nephropathy due to type 2 diabetes are diverse, but large-scale pathologic studies with long-termobservations are limited. Methods. Kidney biopsies and clinical data of 600 patients with type 2 diabetes were collected retrospectively from 13 centres across Japan. Thirteen pathologic findings (nine glomerular lesions, two interstitial lesions and two vascular lesions) were clearly defined and scored. Results. During the observation period, there were 304 composite kidney events [dialysis, doubling of creatinine or reduction of estimated glomerular filtration rate (eGFR) by half], 31 instances of chronic kidney disease (CKD) G5D, 76 cardiovascular events and 73 deaths. The mean observation period was 72.4 months. The distribution of CKD heat map categories for the 600 patients was 103 green or yellow, 149 orange and 348 red. Even in the cases in the green and yellow category, diffuse lesions (81.6%), polar vasculosis (42.6%) and subendothelial space widening (35.1%) were commonly detected. Cox proportional hazard analysis revealed that the presence of nodular lesions [hazard ratio (HR) 21.1, 95% confidence interval (CI) 5.3-84.6], exudative lesions (HR 5.1, 95% CI 1.3-20.3) and mesangiolysis (HR 7.6, 95% CI 2.0-28.8) in cases in the green and yellow category were associated with significantly great impact on composite kidney events after adjustment for clinical risk factors. Conclusions. This nationwide study on kidney biopsy of 600 cases with type 2 diabetes revealed that pathologic findings (presence of nodular lesions, exudative lesions and mesangiolysis) were strong predictors of kidney events in low-risk patients. © The Author 2017.Embargo Period 12 month

Development of Risk Prediction Equations for Incident Chronic Kidney Disease

IMPORTANCE ‐ Early identification of individuals at elevated risk of developing chronic kidney disease  could improve clinical care through enhanced surveillance and better management of underlying health  conditions.  OBJECTIVE – To develop assessment tools to identify individuals at increased risk of chronic kidney  disease, defined by reduced estimated glomerular filtration rate (eGFR).  DESIGN, SETTING, AND PARTICIPANTS – Individual level data analysis of 34 multinational cohorts from  the CKD Prognosis Consortium including 5,222,711 individuals from 28 countries. Data were collected  from April, 1970 through January, 2017. A two‐stage analysis was performed, with each study first  analyzed individually and summarized overall using a weighted average. Since clinical variables were  often differentially available by diabetes status, models were developed separately within participants  with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external  cohorts (N=2,253,540). EXPOSURE Demographic and clinical factors.  MAIN OUTCOMES AND MEASURES – Incident eGFR <60 ml/min/1.73 m2.  RESULTS – In 4,441,084 participants without diabetes (mean age, 54 years, 38% female), there were  660,856 incident cases of reduced eGFR during a mean follow‐up of 4.2 years. In 781,627 participants  with diabetes (mean age, 62 years, 13% female), there were 313,646 incident cases during a mean follow‐up of 3.9 years. Equations for the 5‐year risk of reduced eGFR included age, sex, ethnicity, eGFR, history of cardiovascular disease, ever smoker, hypertension, BMI, and albuminuria. For participants  with diabetes, the models also included diabetes medications, hemoglobin A1c, and the interaction  between the two. The risk equations had a median C statistic for the 5‐year predicted probability of  0.845 (25th – 75th percentile, 0.789‐0.890) in the cohorts without diabetes and 0.801 (25th – 75th percentile, 0.750‐0.819) in the cohorts with diabetes. Calibration analysis showed that 9 out of 13 (69%) study populations had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was  similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 out of 18 (89%) had a slope of observed to predicted risk between 0.80 and 1.25. CONCLUSIONS AND RELEVANCE – Equations for predicting risk of incident chronic kidney disease developed in over 5 million people from 34 multinational cohorts demonstrated high discrimination and  variable calibration in diverse populations

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie