Clinical Impact of Malnutrition According to the Global Leadership Initiative on Malnutrition Criteria Combined With Kidney Dysfunction to Determine Mortality in Inpatients.

OBJECTIVE: The clinical impact of malnutrition based on the Global Leadership Initiative on Malnutrition (GLIM) criteria in patients with kidney dysfunction remains poorly understood. This study investigated the usefulness of GLIM criteria for malnutrition in predicting mortality in patients with kidney dysfunction and different clinical renal states, including no kidney disease (NKD), acute kidney injury (AKI), and chronic kidney disease (CKD). METHODS: This single-center retrospective cohort study included 6,712 patients aged ≥18 admitted between 2018 and 2019. The relationship between the estimated glomerular filtration rate (eGFR) groups, nutritional status based on the GLIM criteria, and the incidence of all-cause mortality was evaluated using a multivariate Cox proportional hazards model. Malnutrition was defined as at least one phenotype (weight loss, low body mass index, or reduced muscle mass) and one etiological criterion (reduced intake/assimilation or disease burden/inflammation). RESULTS: Multivariate Cox proportional hazards model showed that eGFR ≤29 (vs. eGFR: 60-89, adjusted hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.52-2.22), 30-59 (vs. eGFR: 60-89, adjusted HR = 1.40, 95% CI: 1.20-1.64), and ≥90 (vs. eGFR: 60-89, adjusted HR = 1.40, 95% CI: 1.14-1.71), moderate and severe malnutrition (vs. without malnutrition, adjusted HR = 1.38 [1.18-1.62] and 2.18 [1.86-2.54], respectively) were independently associated with the incidence of death. The all-cause mortality rate was higher in patients with malnutrition or eGFR ≤29 (adjusted HR, 3.31; 95% CI: 2.51-4.35) than in patients without malnutrition or eGFR 60-89. Furthermore, moderate and severe malnutrition (vs. no malnutrition) was independently associated with death in patients with NKD, AKI, and CKD. CONCLUSION: Malnutrition based on the GLIM criteria was associated with increased all-cause mortality in inpatients, and malnutrition combined with kidney dysfunction was associated with a higher risk of mortality. Furthermore, patients with NKD, AKI, and CKD showed an association between malnutrition based on GLIM criteria and mortality.

Interleukin-6 blockade reduces salt-induced cardiac inflammation and fibrosis in subtotal nephrectomized mice.

Cardiovascular disease is the most common comorbidity in patients with chronic kidney disease (CKD), affecting both their prognosis and quality of life. Cardiac fibrosis is common in patients with CKD with left ventricular diastolic dysfunction, and it is associated with increased risk of heart failure and mortality. Recent evidence suggests that high salt intake activates immune responses associated with local accumulation of sodium. We reported that high salt intake promotes cardiac inflammation in subtotal nephrectomized (Nx) mice. We investigated the effects of administration of MR16-1, a rat anti-mouse monoclonal interleukin (IL)-6 receptor antibody, in Nx mice with salt loading (Nx-salt). Expression of monocyte chemoattractant protein-1, tumor necrosis factor-α, IL-1ß, and IL-6 mRNAs and macrophage infiltration was significantly reduced in the heart of Nx-salt mice treated with MR16-1 (Nx-salt-MR16-1) compared with Nx-salt mice treated with control rat rat IgG1 (Nx-salt-rat IgG1). Correspondingly, cardiac fibrosis was significantly attenuated in Nx-salt-MR16-1 mice compared with Nx-salt-rat IgG1 mice. Furthermore, in the heart of Nx-salt-MR16-1 mice, expression of mRNA for nicotinamide adenine dinucleotide phosphate oxidase-2, an oxidative stress marker, was significantly downregulated compared with Nx-salt-rat IgG1 mice. Increases in cardiac metabolites, including histidine and γ-butyrobetaine, were also reversed by IL-6 blockade treatment. In conclusion, IL-6 blockade exerts anti-inflammatory, antifibrotic, and partial antioxidative effects in the heart of Nx-salt mice.NEW & NOTEWORTHY In the present study, IL-6 blockade exerted anti-inflammatory, antifibrotic, and partial antioxidative effects on the hearts of mice with CKD on a high-salt diet. Therefore, IL-6 potentially mediates cardiac fibrosis induced by high salt intake in patients with CKD, a finding with therapeutic implications. Of note, the next therapeutic implication may simply be the reinforcement of low-salt diets or diuretics and further research on the anti-inflammatory effects of these measures rather than IL-6 blockade with high-salt diet.

Association of alcohol consumption with the incidence of proteinuria and chronic kidney disease: a retrospective cohort study in Japan.

BACKGROUND: The difference in the clinical impact of alcohol consumption on kidney function based on sex remains to be elucidated. This study aimed to assess the association between the dose of alcohol consumption and the incidence of proteinuria and chronic kidney disease stratified by sex. METHODS: This retrospective cohort study included 26,788 workers (19,702 men and 7086 women) with normal renal function (estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2) at annual health examinations between January 2010 and March 2015 in Japan. The main exposure was alcohol consumption. The primary outcomes were the incidence of proteinuria (dipstick urinary protein ≥ 1) and incidence of low estimated glomerular filtration rate (eGFR; rate < 60 mL/min per 1.73 m2; decreased from the baseline eGFR by 25%). RESULTS: During a median observational period of 4 years (interquartile range: 2-6), 1993 (10.1%) men and 462 (6.5%) women developed proteinuria, whereas 667 (3.4%) men and 255 (3.6%) women developed low eGFR. After adjustment for clinically relevant factors using a Cox proportional hazards model, alcohol consumption of ≥ 46 g/day in females was significantly associated with the incidence of proteinuria (hazard ratio, 1.57; 95% confidence interval, 1.10-2.26) and low eGFR (hazard ratio, 1.62; 95% confidence interval, 1.04-2.53). However, no significant association between alcohol consumption and primary outcomes was observed in men. CONCLUSIONS: In conclusion, daily higher alcohol consumption was significantly associated with a higher incidence of proteinuria and low eGFR among women. Women might be prone to high alcohol consumption with kidney dysfunction.

Time to normalisation of CRP and incidence of relapse in microscopic polyangiitis: A medical records review study in Japan.

OBJECTIVES: Despite the identification of risk factors for relapses in anti-neutrophil cytoplasmic antibody-associated vasculitis, the relationship between changes in C-reactive protein levels after initial treatment and incidence of relapse remains unknown. This study aimed to assess the association between the time taken for normalisation of C-reactive protein levels and the incidence of relapse in Japanese adult patients with microscopic polyangiitis. METHODS: This study included 85 consecutive patients with newly diagnosed microscopic polyangiitis who achieved remission after six months of immunosuppressive treatment at the Aichi Medical University Hospital, between 2009 and 2017. The relationship between the time to normalisation of C-reactive protein after initial immunosuppressive treatment and relapse incidences was evaluated using multivariable Cox proportional hazard models. RESULTS: During the follow-up period, 13 (30.2%), 7 (41.2%), and 16 (64.0%) patients relapsed (P=0.025) within 1-14, 15-28, and ≥29 days of normalisation, respectively. Hazard ratios (95% confidence intervals) of the time to normalisation of C-reactive protein of 1-14, 15-28, and ≥29 days were 1.00 (reference), 2.42 (95%CI: 0.92-6.39), and 3.48 (95%CI: 1.56-7.76), respectively. CONCLUSIONS: A significant association between the time to normalisation of C-reactive protein and relapse incidence in Japanese patients with microscopic polyangiitis was observed.

Safety and utility of the alpha-replacer for treatment of intraluminal obstruction of peritoneal catheters by fibrin clots.

BACKGROUND: The Moncrief-Popovich technique of peritoneal catheter implantation has beneficial effects for peritoneal dialysis (PD) initiation. However, it might increase the risk of peritoneal catheter obstruction by fibrin clots, because the catheter is buried under the skin for several weeks to months. Effects of treatment of intraluminal occlusion of PD catheters with tissue plasminogen activator, recommended by the International Society for Peritoneal Dialysis guidelines/recommendations are reportedly limited. We investigated the effectiveness of the 'alpha-replacer' (JMS, Tokyo, Japan) for PD catheter obstruction. METHODS: We retrospectively analyzed a total of 193 patients in whom PD was initiated. PD catheters were embedded using the Moncrief-Popovich technique in 130 of these patients. We assessed the occurrence rates of peritoneal catheter obstruction and the utility of the alpha-replacer for treating intraluminal catheter occlusion by fibrin clots. RESULTS: Catheter obstruction occurred in eight cases with embedded catheters, one due to omental wrapping and the others due to fibrin clots, in which median catheter burial durations were 477 (interquartile range [IQR], 226-510) days. All catheter obstructions due to fibrin clots were successfully treated with the alpha-replacer, leading to improved catheter drainage. The median amount of contrast agent used in catheterography was 10 (IQR 9-10) mL, which did not adversely affect residual renal function. There were no complications. No recurrence occurred during the observation period (median 111, IQR 55.5-141 months). CONCLUSION: Our results suggest that treatment with the alpha-replacer is a safe and effective treatment option for intraluminal obstruction of PD catheters by fibrin clots.

Association between body mass index and severe infection in older adults with microscopic polyangiitis: a retrospective cohort in Japan.

BACKGROUND: Although previous studies have evaluated risk factors for the incidence of severe infection in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), the relationship between body mass index (BMI) and severe infection in AAV has not been elucidated. We hypothesized that older adults with AAV and a low BMI would be at a higher risk of infection. We therefore investigated the association between underweight status at AAV diagnosis and subsequent occurrence of severe infection in older adults with AAV. METHODS: This single-center retrospective cohort study included 93 consecutive older adults with microscopic polyangiitis (MPA) treated at the Aichi Medical University Hospital in Japan between 2004 and 2018. The relationships between BMI at diagnosis and subsequent first severe infection were assessed using multivariate Cox proportional hazards models. The cumulative probability of the development of the first severe infection was calculated using the Kaplan-Meier method and the log-rank test. The level of statistical significance was set at P <  0.05. RESULTS: During the median follow-up period of 19 (6-53) months, 29 (31.2%) patients developed at least one severe infection. Older age (adjusted hazard ratio [HR] = 2.02, 95% confidence interval [CI]: 1.14-3.52, per 10 years; P =  0.016), low BMI (< 18.5 kg/m2 compared with normal BMI [18.5-23.0 kg/m2], adjusted HR =  2.63, 95% CI: 1.11-6.19; P =  0.027), and use of methylprednisolone pulse therapy (adjusted HR = 2.48, 95% CI: 1.07-5.76; P =  0.034) were found to be significant predictors of severe infection. CONCLUSIONS: Low BMI was associated with a higher risk of severe infection in older adults with MPA, suggesting that careful management may be required to prevent this complication in this vulnerable group. Further studies are needed to elucidate the optimal treatment strategy for these patients.

Relationship between doses of antihypertensive drugs and left ventricular mass index changes in hemodialysis patients in a Japanese cohort.

Left ventricular hypertrophy commonly occurs in dialysis patients and is associated with a risk of developing cardiovascular disease events and all-cause mortality. Although hypertension treatment reduces left ventricular mass index (LVMI) in hemodialysis patients, the relationships of prescription pattern, dose, and changes in the dose of antihypertensive drugs with LVMI have not been completely elucidated. Here, we hypothesized that volume reduction would lead to a decrease in the antihypertensive drug dose and subsequently to a reduction in LVMI; conversely, fluid retention would lead to an increase in the antihypertensive drug use and, subsequently, to LVMI progression. To assess this hypothesis, we investigated the relationship between changes in the dose of antihypertensive drugs and subsequent changes in LVMI in 240 patients who had just started hemodialysis using a retrospective hemodialysis cohort in Japan. Using multiple linear regression analysis, we assessed the association between changes in the antihypertensive drug dose over 1 year after hemodialysis initiation and changes in LVMI during this period. A decrease and an increase in the antihypertensive drug dose were significantly associated with a reduction in LVMI (vs. no change; ß  = - 17.386, p < .001) and LVMI progression (vs. no change; ß  = 16.192, p < .001), respectively. In conclusion, our findings suggested that volume reduction, leading to a decrease in the use of antihypertensive drugs, is a therapeutic strategy in patients undergoing hemodialysis to prevent LVMI progression.

Association between statin use and incidence of relapse in anti-neutrophil cytoplasmic antibody-associated vasculitis: a single-center retrospective cohort study.

Several studies have shown the efficacy of statins for some autoimmune disorders caused by anti-inflammatory and immunomodulatory reactions. However, little information is available about the impact of statins on relapse in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). We performed the first investigation examining whether statin use has an effect on suppressing the first relapse of AAV in Japanese patients with AAV. This single-center retrospective cohort study included 98 consecutive patients with newly diagnosed AAV from Aichi Medical University Hospital, Japan between March 2009 and December 2017. Time to first relapse from the first remission was compared between 36 patients in the statin group and 62 patients in the non-statin group using multivariate Cox proportional hazard models, which were adjusted for clinically relevant factors. During the follow-up period (median, 24 months; interquartile range, 9-50 months), 35 (97.2%) patients in the statin group achieved remission, whereas 56 (90.3%) patients achieved remission in the non-statin group (P = 0.201). After achieving the first remission, 9 (25.7%) patients in the statin group and 29 (51.8%) patients in the non-statin group had at least one relapse. Multivariate Cox proportional hazard models revealed that statin use was significantly associated with a lower incidence of relapse compared with non-statin use (multivariate-adjusted hazard ratio = 0.41, 95% confidence interval: 0.18-0.92; P = 0.031). Patients with statin use were associated with a lower incidence of relapse in AAV. Our results should be assessed in well-designed randomized controlled trials.

Oral candidiasis is a significant predictor of subsequent severe infections during immunosuppressive therapy in anti-neutrophil cytoplasmic antibody-associated vasculitis.

BACKGROUND: Several studies have identified predictors of severe infections in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). However, the development of oral candidiasis (OC) as a predictor of subsequent severe infections has not been evaluated. The aim of this study was to assess the association between OC and subsequent severe infection requiring hospitalization during immunosuppressive therapy in AAV. METHODS: This single-center retrospective cohort study included 71 consecutive patients with newly diagnosed AAV from Aichi Medical University Hospital, Japan, starting immunosuppressive therapy between March 2013 and December 2018. The relationships between OC and subsequent severe infections were assessed using multivariate Cox proportional hazards models, adjusted for clinically relevant factors. RESULTS: During the follow-up period (median, 23 months; interquartile range, 11-51 months), 25 severe infectious episodes occurred in 19 patients (26.8%) and OC occurred in 17 patients (23.9%). A log-rank test showed that the OC group was significantly associated with severe infection (P <  0.001). Multivariate Cox proportional hazards models identified lower serum albumin (per 1 g/dl adjusted hazard ratio (HR)  = 0.38, 95% confidence interval (CI): 0.15-0.85; P  =  0.018), use of methylprednisolone pulse (adjusted HR  =  5.44, 95% CI: 1.54-20.0; P  =  0.010), and OC (adjusted HR  = 5.31, 95% CI: 1.86-15.8; P  =  0.002) as significant predictors of severe infection. Furthermore, a significant effect modification of the use of methylprednisolone pulse on OC was observed (P <  0.001). CONCLUSIONS: OC is one of the predictors of subsequent severe infections. The results suggest the importance of prolonging infection surveillance, especially for patients who developed OC under strong immunosuppressive therapy.

EBV-positive mucocutaneous ulcer arising in rheumatoid arthritis patients treated with methotrexate: Single center series of nine cases.

Methotrexate (MTX) is currently used as first-line anchor drug for rheumatoid arthritis (RA). Therefore, the number of MTX-associated lymphoproliferative disorders, including Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU), has increased. Some aspects of MTX-associated EBVMCU (MTX-EBVMCU), particularly clinical behavior and treatment for RA after MTX cessation, have not been well described. Herein, we report nine cases of MTX-EBVMCU with clinical information regarding RA. Seven of nine patients showed spontaneous regression (SR) after immunosuppressive (IS) cessation. The other two required cytotoxic chemotherapy. Eventually, all achieved complete remission. No patients experienced EBVMCU relapse. Eight patients had RA flare after IS cessation. To control the RA activity, rituximab was administered to three patients. The remaining patients were treated by other agents. Regarding the RA activity, all were in the status of low disease activity or clinical remission. In conclusion, MTX-associated EBVMCU has an indolent clinical course and SR after IS cessation can be expected. After the withdrawal of MTX, the majority of patients experience RA flare and required treatment. In our series, RA was well controlled without reinitiating MTX. Therefore, to prevent the EBVMCU relapse, it might be advisable to avoid MTX reintroduction, and rituximab might be the more preferable agent for RA treatment.

Clostridioides difficile-related toxic megacolon after Cryptococcus neoformans cellulitis: A complex of two rare infections in an immunocompromised host.

A 76-year-old Japanese woman was admitted due to uncontrolled cellulitis of the right lower leg. She had deep vein thrombosis on the right limb. Moreover, she had a long history of rheumatoid arthritis treated with corticosteroids. Skin biopsy and lumbar puncture were performed to diagnose disseminated cryptococcosis. She was administered antifungal agents (liposomal amphotericin B and 5-fluorocytosine). On treatment day 14, debridement was performed, and cryptococcosis was controlled. However, she developed toxic megacolon due to Clostridioides difficile infection (CDI). On day 32, she was transferred to the intensive care unit due to severe acidosis and acute kidney injury secondary to CDI-related toxic megacolon. Vancomycin, metronidazole, and tigecycline were administered for treatment of CDI. After several weeks of intensive care, toxic megacolon was improved, but renal replacement therapy was discontinued according to the patient's will. On day 73, she died of renal failure. We experienced a complex of rare diseases, Cryptococcus neoformans cellulitis and Clostridioides difficile-related toxic megacolon. Both diseases were presumed to be the result of corticosteroid and methotrexate use. Hence, careful monitoring is required when treating immunocompromised hosts to reduce the risk of developing complications.

Successful renal transplantation to a recipient with type II cryoglobulinemia: a case report.

BACKGROUND: Recurrence of glomerulonephritis is an important risk factor for renal graft dysfunction. Cryoglobulinemia is known as a relatively rare cause of renal failure, and doctors are usually hesitant to perform transplantation on a recipient with cryoglobulinemia because of the risk for graft loss. We present a case of renal transplantation on a patient with organ manifestations of type II cryoglobulinemia. CASE PRESENTATION: At the age of 44 years, the patient developed acute kidney injury and purpura on the lower extremities with type II cryoglobulinemia after interferon therapy for hepatitis C virus. Cryoglobulinemic glomerulonephritis was suspected; however, despite immunosuppressive therapy combined with plasmapheresis, she eventually needed hemodialysis treatment. She was referred to us at the age of 49 years for renal transplantation. Cryocrit was 14% and the organ manifestations persisted, including the lower extremity purpura and neurologic symptoms. After monitoring and confirming sufficient suppression of cryoglobulin concentration by immunosuppressive treatment with prednisolone, cyclophosphamide, and rituximab combined with plasmapheresis, the operation was performed. After transplantation, the cryoglobulin concentration was continuously monitored, and plasmapheresis and rituximab infusion were performed as appropriate. Her graft function has remained stable for 2 years and 6 months. CONCLUSION: Our case suggested that a patient with cryoglobulinemia and persistent organ manifestations can receive a renal graft if the cryoglobulin concentration is sufficiently controlled by pretransplant treatment.

Acid-base disturbances in nephrotic syndrome: analysis using the CO2/HCO3 method (traditional Boston model) and the physicochemical method (Stewart model).

BACKGROUND: The Stewart model for analyzing acid-base disturbances emphasizes serum albumin levels, which are ignored in the traditional Boston model. We compared data derived using the Stewart model to those using the Boston model in patients with nephrotic syndrome. METHODS: Twenty-nine patients with nephrotic syndrome and six patients without urinary protein or acid-base disturbances provided blood and urine samples for analysis that included routine biochemical and arterial blood gas tests, plasma renin activity, and aldosterone. The total concentration of non-volatile weak acids (ATOT), apparent strong ion difference (SIDa), effective strong ion difference (SIDe), and strong ion gap (SIG) were calculated according to the formulas of Agrafiotis in the Stewart model. RESULTS: According to the Boston model, 25 of 29 patients (90%) had alkalemia. Eighteen patients had respiratory alkalosis, 11 had metabolic alkalosis, and 4 had both conditions. Only three patients had hyperreninemic hyperaldosteronism. The Stewart model demonstrated respiratory alkalosis based on decreased PaCO2, metabolic alkalosis based on decreased ATOT, and metabolic acidosis based on decreased SIDa. We could diagnose metabolic alkalosis or acidosis with a normal anion gap after comparing delta ATOT [(14.09 - measured ATOT) or (11.77 - 2.64 × Alb (g/dL))] and delta SIDa [(42.7 - measured SIDa) or (42.7 - (Na + K - Cl)]). We could also identify metabolic acidosis with an increased anion gap using SIG > 7.0 (SIG = 0.9463 × corrected anion gap-8.1956). CONCLUSIONS: Patients with nephrotic syndrome had primary respiratory alkalosis, decreased ATOT due to hypoalbuminemia (power to metabolic alkalosis), and decreased levels of SIDa (power to metabolic acidosis). We could detect metabolic acidosis with an increased anion gap by calculating SIG. The Stewart model in combination with the Boston model facilitates the analysis of complex acid-base disturbances in nephrotic syndrome.

A comparative analysis of two interferon-γ releasing assays to detect past tuberculosis infections in Japanese rheumatoid arthritis patients.

OBJECTIVES: To compare the utility of QuantiFERON-TB Gold in tube (QFT-GIT) and T-SPOT.TB assays to detect past tuberculosis infection in Japanese rheumatoid arthritis patients receiving methotrexate. METHODS: We compared the sensitivities and specificities, the rates of indeterminate results, and the rates of positive results in patients with total and CD4-positive lymphocyte counts of both assays simultaneously performed on 68 rheumatoid arthritis patients receiving methotrexate, in whom 33 had evidence of past tuberculosis infection by chest computed tomography and the other had neither history of tuberculosis exposure nor abnormalities in chest computed tomography. RESULTS: The sensitivities, specificities, and the rates of indeterminate results of QFT-GIT were 21.2%, 100%, and 4.4%, and those of T-SPOT.TB were 21.9%, 100%, and 1.5%, respectively. The overall agreement of both assays was good (κ = 0.68). In patients with past tuberculosis infection, there are significant positive linear trends in positive rates of both assays across ranges of larger numbers of total and CD4-positive lymphocyte counts. CONCLUSIONS: Both assays were equally useful with high specificities, but may falsely identify past tuberculosis infection owing to low sensitivities. In patients with low total and CD4-positive lymphocyte counts, both assays might give higher rates of false negative results.

Retrospective analysis of factors predicting end-stage renal failure or death in patients with microscopic polyangiitis with mainly renal involvement.

BACKGROUND: The aim of this study was to identify risk factors for end-stage renal failure (ESRF) or death in Japanese patients with microscopic polyangiitis (MPA) with renal involvement. METHODS: From 54 consecutive patients with systemic vasculitis based on Watt's algorithm, we retrospectively analyzed 39 MPA patients with renal involvement, including 19 (48.7 %) with renal-limited vasculitis. RESULTS: Thirty-three of 39 patients (84.6 %) demonstrated rapidly progressive glomerulonephritis, and 13 (33.3 %) developed ESRF; 8 of 13 required dialysis within 1 week. Thirteen (33.3 %) died during follow-up of more than 12 months, and 7 died during the first 6 months, mainly because of opportunistic infections. Overall survival at 6 and 12 months was 79.5 and 71.1 %, respectively. Serum creatinine levels did not differ significantly between survivors and non-survivors (P = 0.092). The mean Birmingham Vasculitis Activity Score, version 3 (BVAS v.3), was 16.2 ± 6.5, with a renal subscore of over 12 points in 82.1 %, and BVAS v.3 was marginally higher in non-survivors than survivors (P = 0.045). An age- and sex-adjusted Cox proportional hazards analysis demonstrated that neither the serum creatinine level (P = 0.277) nor BVAS v.3 (P = 0.188) at initial diagnosis was a risk factor for overall survival. The baseline serum creatinine cutoff value for discriminating between ESRF and non-ESRF was 4.6 mg/dl, with a sensitivity and specificity of 92.3 and 84.6 %, respectively. CONCLUSIONS: Survival rates do not relate to ESRF in MPA patients with mainly renal involvement. Although patients with ESRF required regular hemodialysis, longer survival can be achieved.

Hypocalcemia immediately after renal transplantation.

BACKGROUND: After renal transplantation (RTX), hypercalcemia, mainly due to persistent hyperparathyroidism, and hypophosphatemia, caused by the improved ability to excrete phosphorus in the renal tubules, are expected. However, immediately after RTX, a transient reduction in serum calcium (Ca) levels has been previously reported, the reason for which is not clear. PATIENTS AND METHODS: In 21 patients receiving ABO compatible living donor kidney transplants, serum levels of Ca, phosphorus, intact parathyroid hormone (iPTH), 1,25-dihydroxyvitamin D, and tacrolimus were measured within three wk after RTX, along with urinary Ca and phosphorus excretion. The immunosuppressive regimen consisted of a three-drug combination including a glucocorticoid, a calcineurin inhibitor, and an antimetabolite agent. RESULTS: Serum Ca levels declined significantly during the first post-operative week. Urinary Ca excretion increased immediately after RTX and gradually normalized. Increased urinary Ca excretion did not correlate with serum levels of iPTH and tacrolimus. CONCLUSIONS: Immediately after RTX, regardless of serum iPTH and tacrolimus levels, transient increases in urinary Ca excretion and hypocalcemia were observed. Administration of glucocorticoids is one potential cause of inappropriate urinary Ca wasting.

Lymphopenia is a risk factor for severe infections in older patients with microscopic polyangiitis: a retrospective cohort study in Japan.

Objective: Previous studies have identified the predictors of severe infections in ANCA-associated vasculitis. However, lymphopenia has not been fully evaluated as a predictor of subsequent severe infections in patients with microscopic polyangiitis (MPA). The aim of this study was to assess the association between lymphopenia and severe infections requiring hospitalization after receiving immunosuppressive therapy for MPA. Methods: This single-centre retrospective cohort study included 130 consecutive patients with newly diagnosed MPA from Aichi Medical University Hospital, Japan, who received immunosuppressive therapy between March 2004 and December 2020. The relationship between lymphopenia and subsequent severe infections was assessed using time-dependent multivariate Cox proportional hazard models adjusted for clinically relevant factors. Results: During the follow-up period (median: 38 months; interquartile range: 15-63 months), 56 severe infectious episodes occurred in 51 patients (39.2%). Time-dependent multivariate Cox proportional hazard analyses identified older age [adjusted hazard ratio (HR) = 1.74 per 10 years, 95% CI: 1.13, 2.67], methylprednisolone pulse therapy (adjusted HR = 2.04, 95% CI: 1.03, 4.02), moderate lymphopenia (vs normal, adjusted HR = 7.17, 95% CI: 3.10, 16.6) and severe lymphopenia (vs normal, adjusted HR = 36.1, 95% CI: 11.8, 110.9) as significant predictors of severe infection. Conclusion: Lymphopenia is a predictor of subsequent severe infections in patients with MPA who receive immunosuppressive therapy. These results suggest the importance of sustained infection surveillance, particularly in older patients who develop lymphopenia during strong immunosuppressive therapy.