Hyperkalemia presentation at a clinic during the cold season.

Familial pseudohyperkalemia (FP) is an underrecognized cause of pseudohyperkalemia, caused by the leaking of potassium from red blood cells. This extracellular shift of potassium is temperature-dependent and occurs when blood samples are stored below room temperature or for a long time, manifesting as apparent hyperkalemia. We report a suspicious case of FP, which demonstrated an apparent seasonal trajectory of serum-potassium levels at the local clinic. At first, laboratory test results did not show an increase in the serum-potassium levels in our tertiary hospital. However, by replicating the clinic's storage conditions, the patient's serum sample showed hyperkalemia only when it was stored at a temperature of 4 °C or 20 °C for 4-8 h. Hyperkalemia was not observed in the patient's sample when it was stored at 37 °C, or in the healthy control's sample at a temperature of 20 °C or 37 °C. When encountering hyperkalemia without an obvious cause and symptoms, physicians should consider pseudohyperkalemia in the differential diagnosis. In particular, if a seasonal trajectory of serum-potassium levels is observed, FP should be suspected as a potential cause of pseudohyperkalemia. Although a genetic test is needed to properly diagnose FP, confirming it by verifying the sample storage conditions or proving it by replicating the test using different storage conditions is easy and very important, as it can prevent unnecessary treatment.

De novo Inflammatory Bowel Disease in Kidney Transplant Recipients: A Single-Center Case Series Study.

Introduction: Gastrointestinal complications are common after solid organ transplantation. New-onset inflammatory bowel disease (IBD) after transplantation (de novo) is a major differential diagnosis of diarrhea after liver transplantation (LT) because of its high incidence in the field. However, the incidence of IBD after kidney transplantation (KT) remains unknown. Methods: This case series comprised six de novo IBD patients who had undergone KT at our hospital from April 1998 to December 2020. In this period, 232 KT recipients were identified. Participants were analyzed based on their colonoscopy diagnoses. Detailed clinical information regarding both KT- and IBD-related symptoms or outcomes was obtained, and we calculated the incidence of de novo IBD from the date of KT. Results: Of the 232 recipients in the median observation period of 6.1 (interquartile range: 2.6, 10.8) years, six recipients (one with Crohn's disease and five with ulcerative colitis) were diagnosed with de novo IBD. The incidence of de novo IBD after KT was 355.8/100,000 person-years (95% confidence interval, 159.8-791.9 per 100,000 person-years). Bloody stools and diarrhea did not always occur, with bloody stools occurring in three and diarrhea in 2 patients at the time of diagnosis. No recipient developed graft failure or extraintestinal complications (e.g., IBD-related nephritis or arthritis). Conclusion: Despite a small sample size, this study's results indicate that the incidence of de novo IBD after KT may be similar to that after LT and higher than that in the general population. Larger studies are required to validate these preliminary findings.

Point-of-Care Ultrasound for the Diagnosis of Congestive Kidney Due to Severe Acidemia: A Case Report.

A 51-year-old woman with mitochondrial myopathy and congestive heart failure with reduced left ventricular ejection fraction was admitted due to loss of appetite and progressive frailty. She presented with acute kidney injury (AKI) and severe acidemia. Given her medical history and physical examination (jugular vein distention was not obvious), prerenal causes (hypovolemia/hypotension) of AKI were considered most likely. However, with a significantly elevated N-terminal pro-b-type natriuretic peptide level of 14,700 pg/mL, a congestive kidney was also considered. Bedside echocardiography showed no evidence of low output syndrome, whereas venous excess ultrasound (VExUS) score was assessed as Grade 2 (moderate congestion). In addition to administering fluids for the suspected prerenal causes (hypovolemia/hypotension), sodium bicarbonate was administered suspecting a negative impact of severe acidemia on cardiac function. With the improvement of acidemia and only a small volume of fluid therapy, there was a rapid improvement in AKI with the normalization of the VExUS score. This suggested that the main cause of AKI was congestive kidney. In this case, VExUS helped us make a correct diagnosis of acidemia-induced congestive kidney rather than hypovolemia as a cause of AKI, leading to the appropriate treatment.

Consequences of kidney donation by age in Japanese living kidney donors: a single-center study.

BACKGROUND: Elderly living kidney donors (LKDs) are becoming increasingly important in countries with a high prevalence of living-donor kidney transplants and an aging society. This study explored the features of elderly LKDs, focusing on their subsequent outcomes. METHODS: This single-center, retrospective, observational study included eligible LKDs who donated their kidneys between April 2008 and July 2022. LKDs were categorized into an elderly (≥70 years at donation) or a non-elderly group (<70 years). We examined pre-operative characteristics and post-operative outcomes, such as kidney function, complications, development of end-stage kidney disease (ESKD), and mortality. RESULTS: Of the 188 LKDs observed for a median of 5.7 years, 31 were in the elderly group (16.5%) and 157 (83.5%) were in the non-elderly group (mean age 72.5 ± 2.7 and 58.2 ± 7.3 years, respectively). No significant differences were observed in hospital stay length or peri-operative complications between groups. Both groups experienced a similar decline in post-donation estimated glomerular filtration rate (eGFR)-approximately 37%. In the elderly group, four LKDs died, and one progressed to ESKD. In the non-elderly group, two LKDs died, and none progressed to ESKD. The cause of death was not strongly suspected to be associated with the donation. CONCLUSIONS: eGFR was maintained even in elderly LKDs post-donation. Prioritizing LKDs' safety is paramount; however, donations from elderly people would be acceptable, considering their life expectancy. This can expand the pool of living kidney donors and address the growing demand for kidney transplants.

The Association between High-Dose Allopurinol and Erythropoietin Hyporesponsiveness in Advanced Chronic Kidney Disease: JOINT-KD Study.

INTRODUCTION: The aim of the study was to explore the association between urate-lowering agents and reduced response to erythropoietin-stimulating agents in patients suffering from chronic kidney disease G5. METHODS: We conducted a cross-sectional, multicenter study in Japan between April and June 2013, enrolling patients aged 20 years or older with an estimated glomerular filtration rate of ≤15 mL/min/1.73 m2. Exclusion criteria encompassed patients with a history of hemodialysis, peritoneal dialysis, or organ transplantation. The patients were categorized into four groups based on the use of urate-lowering drugs: high-dose allopurinol (>50 mg/day), low-dose allopurinol (≤50 mg/day), febuxostat, and no-treatment groups. We used a multivariable logistic regression model, adjusted for covariates, to determine the odds ratio (OR) for erythropoietin hyporesponsiveness, defined by an erythropoietin resistance index (ERI) of ≥10, associated with urate-lowering drugs. RESULTS: A total of 542 patients were included in the analysis, with 105, 36, 165, and 236 patients in the high-dose allopurinol, low-dose allopurinol, febuxostat, and no-treatment groups, respectively. The median and quartiles of ERIs were 6.3 (0, 12.2), 3.8 (0, 11.2), 3.4 (0, 9.8), and 4.8 (0, 11.2) in the high-dose allopurinol, low-dose allopurinol, febuxostat, and no-treatment groups, respectively. The multivariate regression model showed a statistically significant association between the high-dose allopurinol group and erythropoietin hyporesponsiveness, compared to the no-treatment group (OR = 1.98, 95% confidence interval: 1.10-3.57). CONCLUSIONS: Our study suggests that the use of high-dose allopurinol exceeding the optimal dose may lead to hyporesponsiveness to erythropoiesis-stimulating agents.

Chapter 1: Evaluation of kidney function in patients undergoing anticancer drug therapy, from clinical practice guidelines for the management of kidney injury during anticancer drug therapy 2022.

The prevalence of CKD may be higher in patients with cancer than in those without due to the addition of cancer-specific risk factors to those already present for CKD. In this review, we describe the evaluation of kidney function in patients undergoing anticancer drug therapy. When anticancer drug therapy is administered, kidney function is evaluated to (1) set the dose of renally excretable drugs, (2) detect kidney disease associated with the cancer and its treatment, and (3) obtain baseline values for long-term monitoring. Owing to some requirements for use in clinical practice, a GFR estimation method such as the Cockcroft-Gault, MDRD, CKD-EPI, and the Japanese Society of Nephrology's GFR estimation formula has been developed that is simple, inexpensive, and provides rapid results. However, an important clinical question is whether they can be used as a method of GFR evaluation in patients with cancer. When designing a drug dosing regimen in consideration of kidney function, it is important to make a comprehensive judgment, recognizing that there are limitations regardless of which estimation formula is used or if GFR is directly measured. Although CTCAEs are commonly used as criteria for evaluating kidney disease-related adverse events that occur during anticancer drug therapy, a specialized approach using KDIGO criteria or other criteria is required when nephrologists intervene in treatment. Each drug is associated with the different disorders related to the kidney. And various risk factors for kidney disease associated with each anticancer drug therapy.

Acute tubulointerstitial nephritis possibly caused by vedolizumab for ulcerative colitis in a kidney transplant recipient: A case report.

Vedolizumab, which is used to effectively treat ulcerative colitis (UC), is a humanized monoclonal antibody that specifically inhibits α4ß7 integrin on lymphocytes and prevents lymphocyte migration into the intestinal tissues. Herein, we report a case of acute tubulointerstitial nephritis (ATIN) probably caused by vedolizumab in a kidney transplant recipient (KR) with UC. Approximately 4 years after kidney transplantation, the patient developed UC and was treated initially with mesalazine. Treatment continued with the addition of infliximab later; however, he was hospitalized because of poor symptom control and treated with vedolizumab. His graft function declined rapidly after vedolizumab was administered. Allograft biopsy revealed ATIN. Since no evidence of graft rejection was found, vedolizumab-associated ATIN was diagnosed. The patient was treated with steroids, and his graft function improved. Unfortunately, he finally underwent total colectomy considering that UC was refractory to medical treatment. Previously, cases of vedolizumab-induced acute interstitial nephritis have been reported; however, none were associated with KRs. This is the first report of ATIN in KR which was possibly induced by vedolizumab.

Marked hyperkalemia due to inappropriate blood sample storage in two suspected cases of familial pseudohyperkalemia.

We herein report two suspected cases of pseudohyperkalemia who presented with severe hyperkalemia examined at small primary care clinics; however, re-exams at a tertiary care hospital showed normal potassium levels. We reproduced the laboratory examination conditions of the clinics and found that hyperkalemia was due to sampling/storage condition of serum, which is strongly suggestive of familial pseudohyperkalemia (FP). FP is a possible but under-appreciated cause of hyperkalemia, which does not require treatment, so it is important to include FP in the differential diagnosis of hyperkalemia especially in cases with discrepant of serum potassium levels at different settings.

Hyponatremia and mortality in patients undergoing maintenance hemodialysis: Systematic review and meta-analysis.

INTRODUCTION: This systematic review and meta-analysis examined the relationship between hyponatremia and worse outcomes in patients undergoing maintenance hemodialysis. METHODS: The MEDLINE, EMBASE, CENTRAL, and Web of Science databases were used to search for relevant articles. The target population was patients on maintenance hemodialysis (those undergoing hemodialysis for ≥60 days). The defined outcomes were death, cardiovascular disease, cognitive decline, and falls. Meta-analysis was performed with a random-effects model of pairwise comparisons of normonatremia and hyponatremia defined for each study, 1-mmol/L increment of sodium analysis, and dose-response analysis using the sodium concentration defined for each study. This study was registered with PROSPERO (registration number CRD42018087667). RESULTS: Thirteen articles were included. The pairwise analysis revealed that the hazard ratio for all-cause mortality was 1.45 (95% confidence interval, 1.31-1.61). The analysis of 1-mmol/L increment of sodium included six studies with a hazard ratio for all-cause mortality of 0.94 (95% confidence interval, 0.91-0.97) for each 1-mmol/L increase in the serum sodium concentration. In the dose-response analysis, assuming a linear relationship, a sodium increment of 1 mmol/L revealed a hazard ratio for all-cause mortality of 0.97 (95% confidence interval, 0.96-0.98). Other outcomes could not be integrated. CONCLUSIONS: Hyponatremia is associated with all-cause mortality in patients undergoing maintenance hemodialysis. Healthcare providers should pay special attention to even the slightest indication of hyponatremia.

Serological and histopathological assessment of galactose-deficient immunoglobulin A1 deposition in kidney allografts: A multicenter prospective observational study.

BACKGROUND: Recurrent immunoglobulin A (IgA) nephropathy is an important risk factor for kidney allograft loss. However, there is no classification system for IgA deposition in kidney allografts based on serological and histopathological evaluation of galactose-deficient IgA1 (Gd-IgA1). This study aimed to establish a classification system for IgA deposition in kidney allografts based on serological and histological evaluation of Gd-IgA1. METHODS: This multicenter prospective study included 106 adult kidney transplant recipients in whom an allograft biopsy was performed. Serum and urinary Gd-IgA1 levels were investigated in 46 transplant recipients who were IgA-positive and classified into four subgroups according to the presence or absence of mesangial Gd-IgA1 (KM55 antibody) deposits and C3. RESULTS: Minor histological changes without an acute lesion were observed in recipients with IgA deposition. Fourteen (30%) of the 46 IgA-positive recipients were KM55-positive and 18 (39%) were C3-positive. The C3 positivity rate was higher in the KM55-positive group. Serum and urinary Gd-IgA1 levels were significantly higher in KM55-positive/C3-positive recipients than in the other three groups with IgA deposition. Disappearance of IgA deposits was confirmed in 10 of 15 IgA-positive recipients in whom a further allograft biopsy was performed. The serum Gd-IgA1 level at the time of enrollment was significantly higher in recipients in whom IgA deposition continued than in those in whom it disappeared (p = 0.02). CONCLUSIONS: The population with IgA deposition after kidney transplantation is serologically and pathologically heterogeneous. Serological and histological assessment of Gd-IgA1 is useful for identifying cases that should be carefully observed.

Efficacy of pre-emptive kidney transplantation for adults with end-stage kidney disease: a systematic review and meta-analysis.

BACKGROUND: Pre-emptive kidney transplantation (PEKT), i.e., transplantation performed before initiation of maintenance dialysis, is considered an ideal renal replacement therapy because there is no exposure to long-term dialysis therapy. Therefore, we summarized advantages/disadvantages of PEKT to assist in deciding whether kidney transplantation should be performed pre-emptively. METHODS: This study was registered with PROSPERO, CRD42021269163. Observational studies comparing clinical outcomes between PEKT and non-PEKT were included; those involving only pediatric recipients or simultaneous multi-organ transplantations were excluded. The PubMed/MEDLINE, Cochrane Library, and Ichushi-Web databases were searched on 1 August 2021. Studies were pooled using the generic inverse-variance method with random effects model, and risk of bias was assessed using ROBINS-I. RESULTS: Seventy-six studies were included in the systematic review (sample size, 23-121,853; enrollment year, 1968-2019). PEKT patients had lower all-cause mortality (adjusted HR: 0.78 [95% CI 0.66-0.92]), and lower death-censored graft failure (0.81 [0.67-0.98]). Unadjusted RRs for the following outcomes were comparable between the two patient groups: cardiovascular disease, 0.90 (0.58-1.40); biopsy-proven acute rejection, 0.75 (0.55-1.03); cytomegalovirus infection, 1.04 (0.85-1.29); and urinary tract infection, 0.89 (0.61-1.29). Mean differences in post-transplant QOL score were comparable in both groups. The certainty of evidence for mortality and graft failure was moderate and that for other outcomes was very low following the GRADE classification. CONCLUSIONS: The present meta-analysis shows the potential benefits of PEKT, especially regarding patient and graft survival, and therefore PEKT is recommended for adults with end-stage kidney disease.

Allograft adenovirus nephritis accompanied by Crohn's disease in a kidney transplant recipient: a novel case report.

Excessive immunosuppression after kidney transplantation (KT) is often encountered in patients undergoing therapy for anti-rejection or autoimmune disease that requires further treatment using immunosuppressive medications (IMs), including biologic agents. We report a novel case wherein a kidney transplant recipient developed severe acute allograft injury and hemorrhagic cystitis at 4.5 years after KT due to adenovirus nephritis after treatment with infliximab for Crohn's disease. The diagnosis was made based on adenovirus immunohistochemistry staining and urine polymerase chain reaction tests. The patient was successfully treated by reducing IMs and administration of immunoglobulin even though allograft function was eventually partially recovered. When new immunosuppressive agents, particularly biologic agents, are initiated for other diseases in addition to maintenance IMs, the following points need to be regarded: (1) pay attention to opportunistic infections even in the late phase of KT, and (2) maintain communication with other specialists who prescribe biologics to ensure appropriate administration of IMs.