Diagnostic Pitfalls of the Bleeding Origin after a Percutaneous Renal Biopsy: A Report of Two Cases.

A percutaneous renal biopsy (PRB) is a standard procedure for diagnosing renal disease, but can cause bleeding complications. Bleeding after a PRB can be classified as early- or late-onset, depending on the timing of the onset of the bleeding symptoms (<24 h or ≥24 h). We herein report two patients who experienced bleeding complications: one experienced early-onset bleeding from the 12th subcostal artery, and the other experienced late-onset bleeding from an arteriovenous fistula between a branch of the renal artery and renal vein. In both cases, the origin of the bleeding vessel was misjudged during the first examination. We discuss the diagnostic pitfalls of the origin of bleeding after a PRB and propose measures to avoid falling such pitfalls.

Effects of salt reduction education from a salt questionnaire on inter-dialysis weight gain in patients on hemodialysis.

BACKGROUND: Heart failure is the leading cause of death in patients undergoing hemodialysis (HD), with fluid overload being the most common cause. Therefore, it is important for patients undergoing HD to reduce salt intake. We recently developed a highly accurate and simple self-administered salt questionnaire. Using this salt questionnaire, we aimed to determine whether salt intake and inter-HD weight gain decrease when patients with HD are instructed to reduce their salt intake. METHODS: Seventy-eight outpatients at a maintenance HD facility were assessed for dietary salt intake using a salt questionnaire. After one month of dietary guidance, salt intake was assessed again using the salt questionnaire. RESULTS: The mean age of the patients was 72.2 ± 11.9 years; 47 (60.3%) were men, 23 had diabetic nephropathy as the primary disease, and the median HD vintage was 74 months. Salt intake significantly decreased from 8.41 ± 2.43 g/day before the salt questionnaire intervention to 7.67 ± 2.60 g/day after the intervention (p = 0.010). Changes in salt intake before and after the intervention were significantly positively correlated with changes in weight gain before the start of HD sessions with an interval of 2 days (r = 0.24, p = 0.037). Furthermore, changes in salt intake significantly and positively correlated with changes in weight gain after adjusting for age, sex, and dry weight. CONCLUSION: The salt questionnaire may be an effective tool for reducing salt intake and controlling weight gain during HD.

Effect of rehabilitation on renal outcomes after acute kidney injury associated with cardiovascular disease: a retrospective analysis.

BACKGROUND: Acute kidney injury (AKI) incidence is extremely high worldwide, and patients who develop AKI are at increased risk of developing chronic kidney disease (CKD), CKD progression, and end-stage kidney disease (ESKD). However, there is no established treatment strategy for AKI. Based on the idea that exercise has a stabilizing effect on hemodynamics, we hypothesized that rehabilitation would have beneficial renal outcomes in patients with AKI associated with cardiovascular disease. Therefore, the purpose of this study was to determine whether rehabilitation can stabilize hemodynamics and positively impact renal outcomes in patients with AKI associated with cardiovascular disease. METHODS: In total, 107 patients with AKI associated with cardiovascular disease were enrolled in this single-center retrospective study and were either assigned to the exposure group (n = 36), which received rehabilitation at least once a week for at least 8 consecutive weeks, or to the control group (n = 71). Estimated glomerular filtration rate was assessed at baseline before admission, at the lowest value during hospitalization, and at 3, 12, and 24 months after enrolment. Trends over time (group × time) between the two groups were compared using generalized estimating equations. Moreover, congestive status was assessed by amino-terminal pro-B-type natriuretic peptide (NT-proBNP), and the effect of rehabilitation on congestion improvement was investigated using logistical regression analysis. RESULTS: The time course of renal function after AKI, from baseline to each of the three timepoints suggested significant differences between the two groups (p < 0.01). However, there was no significant difference between the two groups at any time point in terms of percentage of patients who experienced a 40% estimated glomerular filtration rate reduction from that at baseline. The proportion of patients with improved congestion was significantly higher in the exposure group compared with that in the control group (p = 0.018). Logistic regression analysis showed that rehabilitation was significantly associated with improved congestion (p = 0.021, OR: 0.260, 95%CI: 0.083-0.815). CONCLUSION: Our results suggest that rehabilitation in patients with AKI associated with cardiovascular disease correlates with an improvement in congestion and may have a positive effect on the course of renal function.

A case of renal sarcoidosis complicated by parotid gland and uterine lesions.

BACKGROUND: Sarcoidosis is a systemic disease that can affect multiple organs. While pulmonary sarcoidosis is most commonly observed, renal sarcoidosis occurs less frequently. We herein report a case of sarcoidosis with an exceptionally rare distribution including renal lesions. CASE PRESENTATION: A 51-year-old Japanese female was referred because of bilateral parotid swelling and renal dysfunction. Computed tomography scan showed the swelling of bilateral kidneys, parotid glands, and uterus. Ga scintigraphy also showed remarkable accumulation in these organs. Renal biopsy and cytological evaluations of parotid gland and uterus were performed and she was diagnosed as sarcoidosis of these organs. Treatment was initiated with prednisolone 40 mg/day and then renal dysfunction subsequently improved. In addition, the swelling of parotid glands and uterus improved and Ga accumulation in each organ had disappeared. CONCLUSION: This is a first case of renal sarcoidosis complicated by parotid glands and uterus lesions. Pathological findings and the reactivity observed in Ga scintigraphy indicated the presence of lesions in these organs.

Anti-contactin 1 Antibody-associated Membranous Nephropathy in Chronic Inflammatory Demyelinating Polyneuropathy with Several Autoantibodies.

A 50-year-old man diagnosed with anti-contactin 1 (CNTN1) antibody-associated chronic inflammatory demyelinating polyneuropathy (CIDP) was referred to our department for the evaluation of proteinuria. A kidney biopsy revealed membranous nephropathy (MN). Immunohistochemistry for CNTN1 revealed positive granular staining along the glomerular basement membrane, confirming anti-CNTN1 antibody-associated MN. Immunofluorescence showed a full-house pattern, and several autoantibodies, such as anti-nuclear antibody, anti-double-strand DNA antibody, and anti-cardiolipin antibody, were detected in the patient's serum. Although limited autoantibodies have been investigated in some of the reported cases, a variety of autoantibodies might be produced in anti-CNTN1 antibody-associated CIDP, accompanied by MN.

Teriparatide-Associated Hypercalcemia Concomitant With Acute Kidney Injury: A Case-Report.

Teriparatide, a recombinant human parathyroid hormone, is an anabolic treatment for osteoporosis with a high risk of fractures. Transient hypercalcemia is an adverse effect of teriparatide and usually resolves within 16h of teriparatide administration owing to its rapid absorption and elimination. Some cases of prolonged hypercalcemia have been reported, but these improved rapidly after teriparatide discontinuation. Here, we describe a rare case of teriparatide-induced hypercalcemia concomitant with acute kidney injury that persisted for four weeks. An 83-year-old woman began taking teriparatide for a vertebral fracture. The patient was immobilized by the fracture. Three weeks later, the patient developed hypercalcemia and acute kidney injury. However, hypercalcemia persisted for four weeks despite the discontinuation of teriparatide and fluid administration. Clinicians should be aware that teriparatide can induce severe hypercalcemia, especially in the setting of immobilization, and that hypercalcemia can persist for more than 3-4 weeks in patients with decreased kidney function.

A Rare Case of Sporadic Medullary Cystic Kidney Disease with Rapidly Progressive Renal Dysfunction and Renal Enlargement Complicated by Idiopathic Nodular Glomerulosclerosis.

An 81-year-old man with hypertension and a history of smoking presented with renal enlargement and progressive renal dysfunction despite no family history of kidney disease. A renal biopsy revealed diffuse tubular, dilated, and atrophic distal tubules with cystic formation and thin irregularities in the tubular basement membrane. Although no known genetic abnormalities were detected, the patient was diagnosed with medullary cystic kidney disease (MCKD). In addition, idiopathic nodular glomerulosclerosis, which is characterized by significant mesangial expansion and accentuated glomerular nodularity and is associated with hypertension and cigarette smoking, was identified as a complication of MCKD. We herein report a rare case of sporadic MCKD with idiopathic nodular glomerulosclerosis.

A survival case of visceral disseminated varicella zoster virus infection in a patient with systemic lupus erythematosus.

BACKGROUND: Visceral disseminated varicella zoster virus (VZV) infection is a rare but life-threatening complication in immunosuppressed patients. Herein, we report a survival case of visceral disseminated VZV infection in a patient with systemic lupus erythematosus (SLE). CASE PRESENTATION: A 37-year-old woman was diagnosed as SLE and initial induction therapy was started. Two months after starting the immunosuppressive therapy consisting of 40 mg of prednisolone (PSL) and 1500 mg of mycophenolate mofetil (MMF) daily, she suddenly developed strong abdominal pain, which was required opioid analgesics, followed by systemic skin blisters, which were diagnosed as varicella. Laboratory findings showed rapid exacerbation of severe liver failure, coagulation abnormalities and increased numbers of blood VZV deoxyribonucleic acid (DNA). Therefore, she was diagnosed as visceral disseminated VZV infection. Multidisciplinary treatment with acyclovir, immunoglobulin and antibiotics was started, the dose of PSL was reduced, and MMF was withdrawn. By their treatment, her symptoms were resolved and she finally discharged. CONCLUSIONS: Our case highlights the importance of a clinical suspicion of visceral disseminated VZV infections, and the necessity of immediate administration of acyclovir and reduced doses of immunosuppressant to save patients with SLE.

A Diagnostic and Therapeutic Dilemma Concerning Exostosin 1/Exostosin 2-associated Lupus-like Membranous Nephropathy with Positive Antinuclear Antibody in an Elderly Man with Various Immune Abnormalities.

Exostosin 1 (EXT1) and exostosin 2 (EXT2)-associated membranous nephropathy (MN) may be associated with active autoimmune disease. We encountered an elderly man who presented with EXT1/EXT2-associated lupus-like MN with full house immune deposits, monoclonal gammopathy of uncertain significance and Sjögren's syndrome. The patient exhibited various other immune abnormalities. Although he did not fulfill the criteria of clinical systemic lupus erythematosus (SLE), he met a stand-alone renal criterion of the Systemic Lupus International Collaborating Clinics (SLICC) 2012. Whether or not a stand-alone renal criterion with EXT1/EXT2 positivity, as in the present patient, can efficiently guide decisions regarding the diagnosis and treatment of SLE remains a clinical dilemma.

Clinical Significance of Trace Element Zinc in Patients with Chronic Kidney Disease.

The trace element zinc is essential for diverse physiological processes in humans. Zinc deficiency can impair growth, skin reproduction, immune function, maintenance of taste, glucose metabolism, and neurological function. Patients with chronic kidney disease (CKD) are susceptible to zinc deficiency, which is associated with erythropoiesis-stimulating agent (ESA) hypo-responsive anemia, nutritional problems, and cardiovascular diseases as well as non-specific symptoms such as dermatitis, prolonged wound healing, taste disturbance, appetite loss, or cognitive decline. Thus, zinc supplementation may be useful for the treatment of its deficiency, although it often causes copper deficiency, which is characterized by several severe disorders including cytopenia and myelopathy. In this review article, we mainly discuss the significant roles of zinc and the association between zinc deficiency and the pathogenesis of complications in patients with CKD.

Association between physical activity and mortality in the Japanese general population with mild to moderate impaired renal function: the Jichi Medical School (JMS) cohort study.

BACKGROUND: The association between physical activity volume or intensity and mortality in general population with impaired renal function is unclear. We assessed these relationships among Japanese residents with impaired renal function. METHODS: We analyzed 638 individuals with estimated creatinine clearance below 60 ml/min in the Jichi Medical School cohort study. Exposures included the daily amount of physical activity converted to the physical activity index (PAI) used in the Framingham study and the activity time for each intensity. Physical activity intensity was classified into sedentary and nonsedentary. Nonsedentary activity was further divided into light-intensity and moderate-to-vigorous physical activity (MVPA). The outcome was all-cause mortality. Quartiles of the exposures were created, and hazard ratios (HRs) were calculated using the Cox proportional hazards model. RESULTS: The mean age of the subjects was 63.3 years, and 72.4% were female. In total, 172 deaths were registered during 11,567 person-years. No significant association was found between PAI and mortality. A significant association was found between long sedentary time and increased mortality (p = 0.042). Regarding nonsedentary activity, the HRs [95% confidence intervals (CIs)] for Q2, Q3, and Q4 versus Q1 were 0.85 (0.55-1.31), 0.67 (0.41-1.08), and 0.90 (0.54-1.45), respectively. In the subdivided analysis for light-intensity activity, the HRs (95% CIs) of Q2, Q3, and Q4 versus Q1 were 0.53 (0.33-0.84), 0.51 (0.34-0.82), and 0.57 (0.34-0.96), respectively. No significant association was found between MVPA and mortality. CONCLUSIONS: Nonsedentary activity, especially light-intensity activity, significantly reduced mortality among residents with impaired renal function.

Long-term effectiveness of a primary care practice facilitation program for chronic kidney disease management: an extended follow-up of a cluster-randomized FROM-J study.

BACKGROUND: Practice facilitation program by multidisciplinary care for primary care physicians (PCPs) is expected to improve chronic kidney disease (CKD) outcomes, but there is no clear evidence of its long-term effectiveness. We have previously performed a cluster-randomized controlled trial for 3.5 years (the Frontier of Renal Outcome Modifications in Japan (FROM-J) study) with two arms-group A without the program and group B with the program. We aimed to assess the long-term effectiveness of the practice facilitation program on CKD outcomes via an extended 10-year follow-up of the FROM-J study. METHODS: We enrolled patients who were in the FROM-J study. The primary composite endpoint comprised cardiovascular disease (CVD), renal replacement therapy initiation and a 50% decrease in the estimated glomerular filtration rate (eGFR). The secondary endpoints were survival rate, eGFR decline rate and collaboration rate between PCPs and nephrologists. RESULTS: The occurrence of the primary composite endpoint tended to be lower in group B (group A: 27.1% versus group B: 22.1%, P = 0.051). Furthermore, CVD incidence was remarkably lower in group B (group A: 10.5% versus group B: 6.4%, P = 0.001). Although both mortality and the rate of eGFR decline were identical between both groups, the eGFR decline rate was significantly better in group B than in group A only in patients with stage G3a at enrollment (group A: 2.35 ± 3.87 mL/min/1.73 m2/year versus group B: 1.68 ± 2.98 mL/min/1.73 m2/year, P = 0.02). The collaboration rate was higher in group B. CONCLUSIONS: The CKD practice facilitation program for PCPs reliably decreases CVD events and may reduce the progression of cases to end-stage kidney disease.

Decline in Walking Independence and Related Factors in Hospitalization for Dialysis Initiation: A Retrospective Cohort Study.

Patients with chronic kidney disease require intervention planning because their physical function declines with worsening disease. Providers can work closely with patients during the induction phase of dialysis. This single-center, retrospective observational study aimed to investigate the rate of decline in walking independence during the induction phase of dialysis and the factors that influence this decline, and to provide information on prevention and treatment during this period. Of the 354 patients who were newly initiated on hemodialysis between April 2018 and January 2022, 285 were included in the analysis. The functional independence measure-walking score was used to sort patients into decreased walking independence (DWI; n = 46) and maintained walking independence (no DWI; n = 239) groups, and patient characteristics were compared. After adjusting for various factors by logistic regression analysis, we observed that age, high Charlson comorbidity index (CCI), C-reactive protein, and emergency dialysis start (EDS) were significant predictors of DWI. Even during the very short period of dialysis induction, as many as 16.1% of patients had DWI, which was associated with older age, higher CCI, higher inflammation, and EDS. Therefore, we recommend the early identification of patients with these characteristics and early rehabilitation.

Rehabilitation of a Patient With Minimal Change Nephrotic Syndrome and Acute Kidney Injury: A Case Report.

Patients with minimal change nephrotic syndrome (MCNS) are prone to loss of motor skills due to urinary protein leakage, steroid myopathy, and other factors. Acute kidney injury (AKI) is a common complication that contributes to the loss of physical function. Rehabilitation is crucial, but its efficacy and safety are unknown. Here we present a case of a patient with MCNS complicated by AKI, who commenced rehabilitation after dialysis was discontinued and experienced improved mobility. The patient, a woman in her 70s, was admitted to our hospital with bilateral lower limb edema and decreased urine output for approximately 5 days. Treatment with prednisolone and furosemide was initiated, but then dialysis was initiated due to AKI. Rehabilitation was started after dialysis was discontinued. The patient's muscle strength and physical activity improved, and her exercise capacity and exercise tolerance improved without adverse effects. Rehabilitation may contribute to the improvement of exercise capacity without worsening renal function and urinary protein in patients with MCNS complicated by AKI.

Deep learning analysis of clinical course of primary nephrotic syndrome: Japan Nephrotic Syndrome Cohort Study (JNSCS).

BACKGROUND: Prognosis of nephrotic syndrome has been evaluated based on pathological diagnosis, whereas its clinical course is monitored using objective items and the treatment strategy is largely the same. We examined whether the entire natural history of nephrotic syndrome could be evaluated using objective common clinical items. METHODS: Machine learning clustering was performed on 205 cases from the Japan Nephrotic Syndrome Cohort Study, whose clinical parameters, serum creatinine, serum albumin, dipstick hematuria, and proteinuria were traceable after kidney biopsy at 5 measured points up to 2 years. The clinical patterns of time-series data were learned using long short-term memory (LSTM)-encoder-decoder architecture, an unsupervised machine learning classifier. Clinical clusters were defined as Gaussian mixture distributions in a two-dimensional scatter plot based on the highest log-likelihood. RESULTS: Time-series data of nephrotic syndrome were classified into four clusters. Patients in the fourth cluster showed the increase in serum creatinine in the later part of the follow-up period. Patients in both the third and fourth clusters were initially high in both hematuria and proteinuria, whereas a lack of decline in the urinary protein level preceded the worsening of kidney function in fourth cluster. The original diseases of fourth cluster included all the disease studied in this cohort. CONCLUSIONS: Four kinds of clinical courses were identified in nephrotic syndrome. This classified clinical course may help objectively grasp the actual condition or treatment resistance of individual patients with nephrotic syndrome.

Predictors of early remission of proteinuria in adult patients with minimal change disease: a retrospective cohort study.

Previous studies reported conflicting results regarding an association between serum albumin concentration and the cumulative incidence of remission of proteinuria in adult patients with minimal change disease (MCD). The present study aimed to clarify the clinical impact of serum albumin concentration and the cumulative incidence of remission and relapse of proteinuria in 108 adult patients with MCD at 40 hospitals in Japan, who were enrolled in a 5-year prospective cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study (JNSCS). The association between serum albumin concentration before initiation of immunosuppressive treatment (IST) and the cumulative incidence of remission and relapse were assessed using multivariable-adjusted Cox proportional hazards models. Remission defined as urinary protein < 0.3 g/day (or g/gCr) was observed in 104 (96.3%) patients. Of 97 patients with remission within 6 month of IST, 42 (43.3%) developed relapse defined as ≥ 1.0 g/day (or g/gCr) or dipstick urinary protein of ≥ 2+. Serum albumin concentration was significantly associated with remission (multivariable-adjusted hazard ratio [95% confidence interval] per 1.0 g/dL, 0.57 [0.37, 0.87]), along with eGFR (per 30 mL/min/1.73 m2: 1.43 [1.08, 1.90]), whereas they were not associated with relapse. A multivariable-adjusted model showed that patients with high eGFR level (≥ 60 mL/min/1.73 m2) and low albumin concentration (≤ 1.5 g/dL) achieved significantly early remission, whereas those with low eGFR (< 60 mL/min/1.73 m2) and high albumin concentration (> 1.5 g/dL) showed significantly slow remission. In conclusion, lower serum albumin concentration and higher eGFR were associated with earlier remission in MCD, but not with relapse.

Sibling cases of gross hematuria and newly diagnosed IgA nephropathy following SARS-CoV-2 vaccination.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination has become a major part of the strategy to reduce Coronavirus disease 2019 (COVID-19) numbers worldwide. To date, vaccinations based on several mechanisms have been used clinically, although relapse of existent glomerulonephritis presenting as gross hematuria, and occurrence of de novo glomerulonephritis have been reported. CASE PRESENTATION: We report the first sibling cases newly diagnosed as immunoglobulin A (IgA) nephropathy after the second dose of SARS-CoV-2 vaccination. 15- and 18-year-old men presented with gross hematuria following the second dose of SARS-CoV-2 vaccine (Pfizer, BNT162b2) received on the same day. Pathological findings of each kidney biopsy specimen were consistent with IgA nephropathy. Gross hematuria in both cases spontaneously recovered within several days. CONCLUSIONS: These cases indicate that SARS-CoV-2 vaccination might trigger de novo IgA nephropathy or stimulate its relapse, and also highlight the necessity of understanding the immunological responses to the novel mRNA vaccines in patients with kidney diseases.

Association between adrenal function and dialysis vintage in hemodialysis patients.

INTRODUCTION: Adrenal insufficiency in hemodialysis patients is commonly encountered in clinical practice. However, its association with end-stage renal disease is unclear. We investigated the relationship between adrenal function and relevant clinical parameters, focusing on dialysis vintage. METHODS: Altogether, 100 maintenance hemodialysis patients were enrolled (age: 69.8 ± 11.8 years, dialysis vintage: 9.4 ± 9.2 years). Basal serum cortisol levels were measured and their associations with relevant clinical parameters were investigated. Subsequently, hormone stimulation tests were performed to assess adrenal function. RESULTS: Basal serum cortisol significantly decreased with an increase in dialysis vintage (< 10 years, 11.9 ± 3.7 µg/dL; 10-19 years, 10.9 ± 2.9 µg/dL; ≥ 20 years, 9.7 ± 3.8 µg/dL). Basal cortisol was negatively correlated with dry weight, ß2-microglobulin, creatinine, and lymphocyte count and positively correlated with brachial-ankle pulse wave velocity. Significant negative correlations were observed between basal cortisol and dialysis vintage after adjusting for confounding variables in the multivariate analysis. Standard adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) stimulation tests were performed in 17 patients. Seven patients were diagnosed with adrenal insufficiency and all of them had a long dialysis vintage (≥ 10 years). According to the rapid ACTH test, cortisol responses were significantly decreased in patients with long dialysis vintage compared to those with short dialysis vintage (< 10 years). Similar findings were observed in ten patients without adrenal insufficiency. The CRH loading test showed similar tendencies, although the differences were not statistically significant. CONCLUSIONS: Adrenal function decreased with an increase in dialysis vintage. Long-term dialysis patients might be susceptible to adrenal insufficiency.